Use of Pyrrolopyridine Compounds for Activating PPAR Receptors and Treatment of Conditions Involving Such Receptors

ABSTRACT

A method of activating PPAR receptors in a subject, said method comprising administering to said subject an effective PPAR receptor activating amount of a pyrrolopyridine compound corresponding to formula (I): 
     
       
         
         
             
             
         
       
     
     wherein R, R 1 , R 2 , R 3 , R 4 , X, Ar and n have defined meanings, or a pharmaceutically acceptable salt thereof, particularly as part of the treatment of a disorder or disease state selected from the group consisting of atherosclerosis, myocardial infarction, hypertension, and cerebral vascular disease.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/040,336, filed Feb. 29, 2008, now U.S. Pat. No. ______, which in turnwas a continuation of international patent application no.PCT/FR2006/050827, filed Aug. 31, 2006, designating the United States ofAmerica and published in French on Mar. 8, 2007, as WO/2007/026104, theentire disclosure of which is incorporated herein by reference. Priorityis claimed based on U.S. provisional patent application No. 60/713,459,filed Sep. 1, 2005 and French patent application no. FR 0510482, filedOct. 14, 2005.

SPECIFICATION

The present invention relates to novel pyrrolopyridine compounds, to aprocess for manufacturing them and to their therapeutic use forpreventing or treating pathologies involving nuclear receptors of PPARtype.

PRIOR ART

In therapeutics, it is known that cardiovascular system diseases are animportant risk factor for health. These diseases are often theconsequence of a high level of cholesterol and/or of triglycerides, andit is thus important to keep these levels below values commonly acceptedby the medical profession.

In the case of cholesterol, it is in particular necessary to evaluatethe amounts of cholesterol associated with various lipoproteins in orderto adapt the treatments so as to lower the levels of LDL-cholesterolwhile at the same time maintaining the levels of HDL-cholesterol. Amongthe known families of compounds used for regulating these parameters arethe statins, which are HMG CoA reductase inhibitors that make itpossible essentially to treat excessively high levels ofLDL-cholesterol, and compounds of the fibrate family, which act byactivating the PPARα (peroxisome proliferator-activated receptor alpha)nuclear receptors and allow the levels of triglycerides and cholesterolto be lowered.

Study of the PPAR nuclear receptors has led to the identification ofthree subtypes, known as PPARα, PPARγ and PPARδ. These variousreceptors, by binding to certain specific fragments of DNA, regulate theexpression of target genes that code for proteins involved in lipidmetabolism regulation mechanisms (see, for example, Current Topics inMedicinal Chemistry, 2003, 3, (14), 1649-1661).

Thus:

-   -   PPARα is expressed essentially in the liver and is involved in        fatty acid catabolism by regulating β- and ω-oxidation (J.        Lipid. Res. (1996) 37, 907-925);    -   the PPARγs are expressed mainly in adipose tissue and are        involved in glycemia regulation mechanisms;    -   PPARδ is expressed ubiquitously, but is mainly present in the        kidneys, skeletal muscle, the heart and the intestine. Like the        other receptors of PPAR type, PPARδ forms a heterodimer with RXR        (retinoid X receptor) and is then capable of binding to certain        target gene elements of the nucleus and of controlling        transcription factors. Among the various studies devoted to this        nuclear receptor, it has been demonstrated, for example, that        activation of PPARδ makes it possible to increase the level of        HDL-cholesterol in db/db mice (FEBS Letters (2000), 473,        333-336) and obese insulin-dependent Rhesus monkeys, and        promotes the flow of cholesterol via Apo A1 in human THP-1        cells, (Proc. Nat. Ac. Sci. USA (2001), 98, 5306-5311).

The treatment of type 2 non-insulin-dependent diabetes remainsunsatisfactory, despite the arrival on the market of numerous oralhypoglycemiant derivatives for facilitating the secretion of insulin andfor promoting its action on the target peripheral tissues. PPARγagonists are generally described for improving sensitivity to insulin,as has already been observed with the thiazolidinediones (TZD).

Novel PPAR agonists are developed in the treatment of type 2 diabetesand/or dyslipidemia. Among the novel PPAR agonists, several areactivators of at least two of the three subtypes PPAR α, δ and γ.

The increase in the frequency of these pathologies calls for thedevelopment of novel therapeutic agents that are active in the case ofthese diseases: compounds having excellent hypoglycemiant andhypolipidemiant activity while avoiding the side effects observed withthiazolidinediones are consequently very useful in the treatment and/orprophylaxis of type 2 non-insulin-dependent diabetes for reducingperipheral insulin resistance and normalizing glycemia.

Following the study of these various nuclear receptors, it appears thatcompounds that are agonists simultaneously of two, and preferably ofthree, PPAR receptor subtypes, might have an extremely advantageouspharmacological profile for simultaneously treating pathologies such ashyperlipidemia, hypercholesterolemia and diabetes, and also variouscardiovascular system diseases that are the consequence of a metabolicsyndrome.

The present invention concerns PPAR receptor activators or modulators.These compounds satisfy the pharmacological criteria mentioned above.

Among the prior art documents mentioning similar compounds, knownexamples include documents WO 97/28149, WO 04/060871, WO 05/016335 andWO 05/016881, which describe PPARδ receptor agonists, document WO01/60807, which describes PPARα agonists, or documents WO 05/009958 andWO 05/056522, which propose indole compounds that are active on the PPARreceptors.

Mention will also be made of documents WO 02/071827 and Bioorganic andMed. Chem. Letter Vol. 14 (11) pp. 259-2763 (06/2004), which describederivatives that are RXR receptor modulators and their therapeutic usefor treating pathologies involved in metabolic syndrome.

Moreover, various pyrrolopyridine compounds have been described in theprior art, for instance certain intermediates disclosed in document WO98/25611, the claimed compounds of which are active against thrombosis.

SUMMARY OF THE INVENTION

The present invention relates to novel pyrrolopyridine derivatives thatare PPAR activators, and are chosen from

i) the compounds of formula:

in which:R₁ and R₂ each independently represent a hydrogen atom, a halogen atom,a C₁-C₄ alkyl or C₁-C₄ alkoxy group or a CF₃ group,R₃ and R₄ each independently represent a hydrogen atom or a C₁-C₄ alkylgroup,R represents a hydrogen atom or a C₁-C₃ alkyl group,n=1, 2 or 3X represents a single bond or an oxygen atom,Ar represents an aromatic or heteroaromatic nucleus chosen from phenyl,pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, furyl, thienyl,pyrrolyl, pyridyl, biphenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl,isoquinolyl, quinolyl, 1,2,3,4-tetrahydroquinolyl, benzimidazolyl,benzopyrazinyl, indolyl, 2,3-dihydroindolyl, benzofuryl,2,3-dihydrobenzofuryl, benzothiazolyl, benzothiadiazolyl,benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl, 1,3-benzodioxolyl,2,3-dihydrobenzodioxinyl, imidazothiazolyl and benzoxazolyl groups,optionally substituted with one or more (for example 2 or 3)substituents chosen from halogen atoms and C₁-C₆ alkyl, C₁-C₄ alkoxy,trifluoromethyl, trifluoromethoxy, nitro, acetyl, acetylamino anddialkylamino groups, in which each alkyl group contains from 1 to 3carbon atoms or amino, or oxazolyl, thiazolyl, pyrazolyl, pyrrolidinyl,pyridyl, pyrimidinyl, methylpyrimidinyl or morpholinyl heterocycles,ii) pharmaceutically acceptable salts thereof.

According to a second aspect, the invention relates to theabovementioned compounds for their use as pharmacologically activesubstances, and also to the pharmaceutical compositions containing from.

In addition, the invention relates to the use of at least one compoundof formula (I) or a pharmaceutically acceptable salts thereof as anactive principle for the preparation of a medicament intended for atherapeutic use, especially for combating hypercholesterolemia,hyperlipidemia, hypertriglyceridemia, dyslipidemia, insulin resistance,diabetes or obesity, and also cardiovascular diseases that are theconsequence of an imbalance of serum lipoproteins. The compoundsaccording to the invention are also useful as active principles formedicaments for preventing or treating diseases associated withendothelial dysfunction, atherosclerosis, myocardial infarction,hypertension, cerebral vascular problems, certain inflammatory diseases,for instance rheumatoid arthritis, and neurodegenerative diseasesespecially such as Alzheimer's disease or Parkinson's disease.

DETAILED DESCRIPTION

In the present description, the term “C₁-C_(n) alkyl group” (n being aninteger) means a linear, branched or partially or totally cyclichydrocarbon-based chain containing from 1 to n carbon atoms, the cyclicpart containing at least 3 carbon atoms. For example, and withoutlimitation, a C₁-C₆ alkyl group may be a methyl, ethyl, propyl, butyl,pentyl, hexyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl,1,1-methylethyl, 1-methylbutyl, 1,1-dimethylpropyl, 1-methylpentyl,1,1-dimethylbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl orcyclopentylmethyl group. The term “C₁-C_(n) alkoxy group” (n being aninteger) means a group RO— in which R represents an alkyl groupcontaining from 1 to n carbon atoms as defined previously. The term“halogen” means a fluorine, chlorine, bromine or iodine atom, fluorineand chlorine atoms being preferred.

The compounds of formula (I) in which R represents a hydrogen atom arecarboxylic acids that may be used in the form of free acids or in theform of salts, said salts being obtained by combining the acid with apharmaceutically acceptable nontoxic mineral or organic base. Among themineral bases that may be used are, for example, sodium hydroxide,potassium hydroxide, magnesium hydroxide and calcium hydroxide. Amongthe organic bases that may be used are, for example, amines, aminoalcohols, basic amino acids such as lysine or arginine, or compoundsbearing a quaternary ammonium function, for instance betaine or choline.

The compounds of formula (I) in which the substituents R₃ and R₄ aredifferent have an asymmetric center. For these compounds, the inventioncovers both the racemic compound and each of the optical isomersconsidered separately.

One particular family of compounds according to the invention comprisesthe compounds of the abovementioned formula I in which:

R₁ and R₂ each independently represent a hydrogen atom, a halogen atomor a CF₃ group,R₃ and R₄ each independently represent a hydrogen atom or a C₁-C₄ alkylgroup,R represents a hydrogen atom or a C₁-C₃ alkyl group,n=1 or 2,X represents a single bond or an oxygen atom,Ar represents an aromatic or heteroaromatic nucleus chosen from phenyl,naphthyl, benzothiazolyl, 3,4-dihydro-1,4-benzoxazinyl,1,3-benzodioxolyl, 2,3-dihydrobenzodioxinyl and benzoxazolyl groups,optionally substituted with one or more substituents chosen from C₁-C₆alkyl, C₁-C₄ alkoxy and amino groups.

Among the compounds of formula I according to the invention, thepreferred compounds are those

in which:R₁ and R₂ each independently represent a hydrogen atom, a halogen atom,a C₁-C₄ alkyl or C₁-C₄ alkoxy group or a CF₃ group,R₃ and R₄ each independently represent a hydrogen atom or a C₁-C₄ alkylgroup,R represents a hydrogen atom or a C₁-C₃ alkyl group,n=1, 2 or 3X represents a single bond or an oxygen atom,Ar represents an aromatic or heteroaromatic nucleus chosen from phenyl,pyridyl, biphenyl, naphthyl, quinolyl, benzopyrazinyl, indolyl,2,3-dihydroindolyl, benzofuryl, 2,3-dihydrobenzofuryl, benzothiazolyl,benzothiadiazolyl, benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl,1,3-benzodioxolyl, 2,3-dihydrobenzodioxinyl, imidazothiazolyl andbenzoxazolyl groups, optionally substituted with one or more (forexample 2 or 3) substituents chosen from halogen atoms and C₁-C₆ alkyl,C₁-C₄ alkoxy, trifluoromethyl, trifluoromethoxy, nitro, acetyl,acetylamino and dialkylamino groups, in which each alkyl group containsfrom 1 to 3 carbon atoms or amino, or oxazolyl, thiazolyl, pyrazolyl,pyrrolidinyl, pyridyl, pyrimidinyl, methylpyrimidinyl or morpholinylheterocycles.

Among the compounds according to the invention, preferred compounds arealso those in which Ar represents a phenyl group. The compounds in whichR₁ represents a chlorine atom or a trifluoromethyl group are alsopreferred.

The compounds according to the invention may be prepared according to afirst process that consists in:

a) performing a halogenation reaction, preferentially an iodinationreaction, of an aminopyridine of formula

in which:R₁ and R₂ each independently represent a hydrogen atom, a chlorine,bromine or fluorine atom, a C₁-C₄ alkyl or C₁-C₄ alkoxy group or atrifluoromethyl group,using a halogenating agent, for instance iodine in the presence ofsilver sulfate or benzyltrimethylammonium dichloroiodate, in a solvent,such as dichloromethane or an aliphatic alcohol, at room temperature,for 5 to 24 hours to obtain the compound of formula

in which:R₁ and R₂ conserve the same meaning as in the starting compounds;

b) reacting, according to the Sonogashira reaction (see, for example:Tet. Lett., 1975, 4467), the compound of formula III with an acetylenicderivative of formula

in which:n=1, 2 or 3;R₃ and R₄ each independently represent a hydrogen atom or a C₁-C₄ alkylgroup;R represents a C₁-C₃ alkyl group;X represents a single bond or an oxygen atom;in the presence of cuprous iodide, a palladium-based catalyst, forinstance tetrakis(triphenylphosphine)palladium ordichloro-bis(triphenylphosphine)palladium, and an organic base, forinstance triethylamine, in a solvent, for instance dimethylformamide(DMF), at a temperature of between 0 and 60° C. for 2 to 24 hours, toobtain the compound of formula

in which:

R₁, R₂, n, X, R₃, R₄ and R conserve the same meaning as in the startingcompounds;

c) reacting the compound of formula V with an arylsulfonyl chloride offormula

Ar—SO₂—Cl  (VI)

in which:Ar represents an aromatic or heteroaromatic nucleus chosen from phenyl,pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, furyl, thienyl,pyrrolyl, pyridyl, biphenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl,quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, benzimidazolyl,benzopyrazinyl, indolyl, 2,3-dihydroindolyl, benzofuryl,2,3-dihydrobenzofuryl, benzothiazolyl, benzothiadiazolyl,benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl, 1,3-benzodioxolyl,2,3-dihydrobenzodioxinyl, imidazothiazolyl and benzoxazolyl groups,optionally substituted with one or more (for example 2 or 3)substituents chosen from halogen atoms and C₁-C₆ alkyl, C₁-C₄ alkoxy,trifluoromethyl, trifluoromethoxy, nitro, acetyl, acetylamino anddialkylamino or amino groups, or oxazolyl, thiazolyl, pyrazolyl,pyrrolidinyl, pyridyl, pyrimidinyl, methylpyrimidinyl or morpholinylheterocycles, in the presence of pyridine, optionally in a solvent, suchas dichloromethane, at room temperature, for 10 to 120 minutes, toobtain the compound of formula

in which:R₁, R₂, n, X, R₃, R₄, R and Ar conserve the same meaning as in thestarting compounds;

d) performing a cyclization of the compound of formula VII, for examplevia the action of copper II acetate (see, for example J. Org. Chem.,2004, 69 (4), 1126-1136), in a solvent, such as 1,2-dichloroethane, at atemperature close to the reflux temperature of the solvent, for 4 to 24hours, to obtain the compound of formula

in which:R₁, R₂, n, X, R₃, R₄, R and Ar conserve the same meaning as in thestarting compounds;

e) if necessary, hydrolyzing the ester function of the compound offormula Ia, for example via the action of a mineral base, such as sodiumhydroxide or lithium hydroxide, according to procedures that are wellknown to those skilled in the art, to obtain, after acid treatment, thecompound of formula I in the form of the free acid:

According to the first variant of the preparation process, the compoundsof formula I may be obtained via a series of reactions consisting in:

a) reacting the compound of formula (III)

as obtained above, with an arylsulfonyl chloride of formula

Ar—SO₂—Cl  (VI)

in which:Ar represents an aromatic or heteroaromatic nucleus chosen from phenyl,pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, furyl, thienyl,pyrrolyl, pyridyl, biphenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl,quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, benzimidazolyl,benzopyrazinyl, indolyl, 2,3-dihydroindolyl, benzofuryl,2,3-dihydrobenzofuryl, benzothiazolyl, benzothiadiazolyl,benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl, 1,3-benzodioxolyl,2,3-dihydrobenzodioxinyl, imidazothiazolyl and benzoxazolyl groups,optionally substituted with one or more (for example 2 or 3)substituents chosen from halogen atoms and C₁-C₆ alkyl, C₁-C₄ alkoxy,trifluoromethyl, trifluoromethoxy, nitro, acetyl, acetylamino anddialkylamino or amino groups, or oxazolyl, thiazolyl, pyrazolyl,pyrrolidinyl, pyridyl, pyrimidinyl, methylpyrimidinyl or morpholinylheterocycles,in a solvent, for instance dimethylformamide, preferably in the presenceof an aprotic base, for instance pyridine, at room temperature and for 1to 12 hours, to obtain the compound of formula (VIII)

in which:R₁, R₂ and Ar conserve the same meaning as in the starting compounds;

b) reacting the compound of formula VIII with an acetylenic derivativeof formula

in which:n=1, 2 or 3;R₃ and R₄ each independently represent a hydrogen atom or a C₁-C₄ alkylgroup;R represents a C₁-C₃ alkyl group;X represents a single bond or an oxygen atom;under conditions similar to those described for step b) of the abovegeneral process, to obtain the compound of formula

in which R₁, R₂, n, X, R₃, R₄, R and Ar conserve the same meaning as inthe starting compounds;

c) if necessary, hydrolyzing the ester function of the compound offormula Ia, for example via the action of a mineral base, such as sodiumhydroxide or lithium hydroxide, according to procedures that are wellknown to those skilled in the art, to obtain, after acid treatment, thecompound of formula I in the form of the free acid:

The compounds of the invention in the form of salts of an acid offormula Ib with a mineral or organic base may be obtainedconventionally, by using methods that are well known to those skilled inthe art, for example by mixing stoichiometric amounts of the acid andthe base in a solvent, for instance water or an aqueous-alcoholicmixture, and then freeze-drying the solution obtained.

In some of the reaction steps described above, it is advantageouslypossible to replace the traditional heating methods with microwaveheating using reactors adapted to this mode of reaction. In this case, aperson skilled in the art will understand that the “heating” times willbe considerably reduced in comparison with the times required forstandard heating.

The examples that follow the preparation of compounds according toformula (I) will allow the invention to be understood more clearly.

In these examples, which do not limited the scope of the invention, theterm “preparation” denotes examples describing the synthesis ofintermediate compounds and the term “examples” are examples describingthe synthesis of compounds of formula (I) according to the invention.Among the abbreviations, “mM” means millimoles, THF meanstetrahydrofuran, DMF means dimethylformamide, DME means1,2-dimethoxyethane, DCM means dichloromethane and PdCl₂dppf meansdichloro-1,1′-bis(diphenylphosphino)-ferrocenepalladium(II).

The melting points are measured on a Köfler block or using a Mettlermachine and the nuclear magnetic resonance spectral values arecharacterized by the chemical shift calculated relative to TMS, by thenumber of protons associated with the signal and by the shape of thesignal (s for singlet, d for doublet, dd for doubled doublet, t fortriplet, q for quartet, quint. for quintet and m for multiplet). Theworking frequency and the solvent used are indicated for each compound.Room temperature is 20° C.±5° C.

Preparation I 3-Amino-6-chloro-2-iodopyridine

23.2 g (180.5 mM) of 5-amino-2-chloropyridine are mixed in 70 ml ofdichloro-methane (DCM) and 180 ml of methanol, and 21.6 g (216 mM) ofcalcium carbonate and 75.3 g (226 mM) of benzyltrimethylammoniumdichloroiodate are added. The reaction mixture is stirred at roomtemperature for 16 hours, and then filtered to remove the mineral salts.The filtrate is diluted with water and extracted with DCM. The organicphase obtained is washed with sodium chloride solution, and then withsaturated sodium thiosulfate solution, dried over magnesium sulfate andconcentrated under reduced pressure. An oil is obtained, which ispurified by chromatography on silica gel, eluting with acyclohexane/ethyl acetate mixture (80/20 and then 70/30; v/v). 13.9 g ofthe expected product are thus obtained in the form of an orange-coloredsolid (yield=30%).

m.p.=148° C.

Preparation II 3-[Di(benzenesulfonyl)amino]-6-chloro-2-iodopyridine

A mixture of 13.75 g (54 mM) of the compound according to Preparation Iand 27.6 ml (216 mM) of benzenesulfonyl chloride in 30 ml of pyridine isstirred for 60 hours at room temperature. The reaction mixture is thendiluted with water and extracted several times with ethyl acetate. Theorganic phase is washed with N hydrochloric acid solution, and then withsodium chloride solution, dried over magnesium sulfate and concentratedunder reduced pressure. The expected compound is obtained in the form ofa beige-colored solid (yield=96%).

m.p.=231° C.

Preparation III N-(6-Chloro-2-iodo-3-pyridyl)benzenesulfonamide

15.46 g (29 mM) of the compound according to Preparation II are mixed in170 ml of dioxane and 77 ml of aqueous 3 M potassium hydroxide solutionare added. The reaction mixture is stirred under gentle reflux of thesolvent for 1 hour, and then concentrated under reduced pressure. Abeige-colored solid is obtained, which is suspended in 200 ml of water.The mixture is acidified to pH 4 approximately by adding hydrochloricacid and is then extracted with dichloromethane (DCM). The organic phaseis dried over magnesium sulfate and then concentrated under reducedpressure. 10.32 g of the expected product are thus obtained in the formof a beige-colored solid (yield=91%).

m.p.=132° C.

Example 15-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid,methyl ester

10.32 g (26.2 mM) of the compound according to Preparation III, 30 ml ofdimethylformamide, 460 mg (0.65 mM) ofdichlorobis(triphenylphosphine)palladium, 250 mg (1.3 mM) of cuprousiodide and 20 ml of diethylamine are mixed together. 3.5 g (31.25 mM) ofmethyl 4-pentynoate are then added with stirring, at room temperature,and the reaction mixture is stirred for 1 hour under gentle reflux ofthe solvent. The reaction mixture is then diluted with water andextracted several times with ethyl acetate. The organic phase is washedwith sodium chloride solution, dried over magnesium sulfate andconcentrated under reduced pressure. The brown oil obtained is purifiedby chromatography on silica gel, eluting with a cyclohexane/ethylacetate mixture (8/2; v/v). 8.02 g of the expected product are thusobtained in the form of a yellow solid (yield: 81%).

m.p.=108-115° C.

Example 25-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid

1.5 g (4 mM) of the ester obtained according to Example 1 are mixed in 5ml of tetrahydrofuran and a solution of 332 mg (7.9 mM) of lithiumhydroxide (LiOH.H₂O) in 4 ml of water is added. The reaction medium isstirred for 2 hours at room temperature and then acidified to pH 3 withhydrochloric acid and extracted with DCM. The organic phase is driedover magnesium sulfate and concentrated under reduced pressure. Aslightly yellow oil is obtained, which crystallizes in the form of awhite solid (yield=77%).

m.p.=185-187° C.

Preparation IV 3-Amino-2-iodo-6-(trifluoromethyl)pyridine

3.85 g (12.3 mM) of silver sulfate are added, with stirring and at roomtemperature, to a solution of 2 g (12.3 mM) of5-amino-2-(trifluoromethyl)pyridine in 100 ml of ethanol. 3.13 g ofiodine are then added and the reaction mixture is stirred at roomtemperature for 24 hours. The solid in suspension in the medium isremoved by filtration and the filtrate is concentrated under reducedpressure. The evaporation residue is taken up in 200 ml ofdichloromethane and washed with 5% sodium hydroxide solution, and thenwith water and dried over magnesium sulfate. The solution obtained isconcentrated under reduced pressure and 3.42 g of the expected compoundare thus obtained in the form of a pink solid (yield=96%).

m.p.=127° C.

Preparation V 6-(3-Amino-6-chloro-2-pyridyl)-5-hexynoic acid, methylester

5 g (19.6 mM) of the compound according to Preparation I, 20 ml ofdimethylformamide, 345 mg (0.49 mM) ofdichlorobis(triphenylphosphine)palladium, 187 mg (0.98 mM) of cuprousiodide and 10 ml of diethylamine are mixed together. 2.97 g (23.5 mM) ofmethyl 5-hexynoate are then added with stirring, at room temperature,and the reaction mixture is stirred for 1 hour under gentle reflux ofthe solvent. The reaction mixture is then diluted with water andextracted several times with ethyl acetate. The organic phase is washedwith sodium chloride solution, dried over magnesium sulfate andconcentrated under reduced pressure. The residual oily compound obtainedis purified by chromatography on silica gel, eluting with acyclohexane/ethyl acetate mixture (9/1; v/v). 4.15 g of the expectedproduct are thus obtained in the form of an oil (yield: 84%).

¹H NMR (300 MHz, DMSO) δ: 1.83 (quint., 2H); 2.47 (t, 2H); 2.54 (t, 2H);3.60 (s, 3H); 5.63 (s, 2H); 7, 10 (s, 2H).

Preparation VI6-[3-[(6-Benzothiazolylsulfonyl)amino]-6-chloro-2-pyridyl]-5-hexynoicacid, methyl ester

A solution of 1 g (4 mM) of the compound according to Preparation V in10 ml of pyridine is prepared and 1.1 g (4.7 mM) of6-benzothiazolesulfonyl chloride are added. The mixture is stirred for 3hours at room temperature and then diluted with water and extracted withethyl acetate. The organic phase is washed twice with N hydrochloricacid solution, and then with water, dried over magnesium sulfate andconcentrated under reduced pressure. The residual oil is purified bychromatography on silica gel, eluting with a cyclohexane/ethyl acetatemixture (7/3; v/v). 1.07 g of the expected compound are thus obtained inthe form of a yellow solid (yield=60%).

m.p.=134° C.

Example 31-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A mixture of 1 g (2.22 mM) of ester according to Preparation VI in 3 mlof 1,2-dichloroethane is prepared in a microwave reactor tube, and 403mg (2.22 mM) of copper (cupric) acetate are added. The mixture is heatedby microwave at 150° C. for 30 minutes, and then cooled, diluted with 6ml of dichloromethane and filtered through Whatman paper. The filtrateis concentrated under reduced pressure and the crude product is purifiedby chromatography on silica gel, eluting with a cyclohexane/ethylacetate mixture (8/2; v/v). 500 mg of the expected compound are thusobtained in the form of a yellow solid (yield=50%).

m.p.=55° C.

Example 41-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 3, the expected product isobtained in the form of a beige-colored solid (yield=95%).

m.p.=178° C.

Preparation VIIN-[2-Iodo-6-(trifluoromethyl)-3-pyridyl]benzenesulfonamide

7 g (40 mM) of benzenesulfonyl chloride are gradually added, withstirring and at room temperature, to a solution of 2.88 g (10 mM) of thecompound according to Preparation IV in 25 ml of pyridine. The reactionmixture is stirred at room temperature for 24 hours, and then pouredinto 300 ml of ice-cold N hydrochloric acid. The precipitate obtained isseparated out by filtration and washed with water on the filter, andthen stirred in a flask with 40 ml of dioxane and 10 ml of aqueous 3 Mpotassium hydroxide solution, under gentle reflux of the solvent, for 2hours. This reaction mixture is cooled, diluted with 300 ml of water,acidified to pH 1.5 approximately with concentrated hydrochloric acid,and is then extracted with dichloromethane. The organic phase obtainedis washed with water and then dried over magnesium sulfate andconcentrated under reduced pressure. 3.7 g of the expected product arethus obtained in the form of a white solid (yield=89%).

m.p.=131° C.

Preparation VIII 5-[3-Amino-6-chloro-2-pyridyl]-4-pentynoic acid, methylester

By working in a manner similar to that of Preparation V, starting withthe methyl ester of 4-pentynoic acid, the expected product is obtainedin the form of a yellow solid (yield=77%).

m.p.=96-100° C.

By working in a manner similar to that of Preparation VI, starting withthe appropriate sulfonyl chlorides, the following compounds areobtained:

Preparation IX6-[3-[(1,3-Benzodioxol-5-ylsulfonyl)amino]-6-chloro-2-pyridyl]-5-hexynoicacid, methyl ester

Brown solid, yield=91%.

m.p.=123° C.

Preparation X6-[3-[(2-Amino-5-benzothiazolylsulfonyl)amino]-6-chloro-2-pyridyl]-5-hexynoicacid, methyl ester

White solid, yield=37%.

m.p.=66-72° C.

Preparation XI6-[6-Chloro-3-[(3,5-dimethylphenyl)sulfonylamino]-2-pyridyl]-5-hexynoicacid, methyl ester

Orange oil, yield=98%.

¹H NMR (300 MHz, DMSO) δ: 1.74 (quint., 2H); 2.30 (s, 6H); 2.40 (t, 2H);2.42 (t, 2H); 3.61 (s, 3H); 7.28 (s, 1H); 7.33 (s, 2H); 7.45 (d, 1H);7.70 (d, 2H); 10.07 (s, 1H).

Preparation XII6-[6-Chloro-3-[(2,5-dimethoxyphenyl)sulfonylamino]-2-pyridyl]-5-hexynoicacid, methyl ester

Orange solid, yield=84%.

m.p.=78-82° C.

Preparation XIII6-[6-Chloro-3-[(1-naphtalenyl)sulfonylamino]-2-pyridyl]-5-hexynoic acid,methyl ester

Orange solid, yield=98%.

m.p.=117° C.

Preparation XIV6-[6-Chloro-3-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl-amino]-2-pyridyl]-5-hexynoicacid, methyl ester

Brown oil, yield=74%.

¹H NMR (300 MHz, DMSO-d₆) δ: 1.75 (quint., 2H); 2.41 (m, 4H); 2.78 (s,3H); 3.28 (m, 2H); 3.61 (s, 3H); 4.27 (m, 2H); 6.78 (d, 1H); 6.88 (s,1H); 6.89 (d, 1H); 7.44 (d, 1H); 7.71 (d, 1H); 9.80 (s, 1H).

By working in a manner similar to that of Preparation VI, starting withthe ester according to Preparation Viii and the appropriate sulfonylchlorides, the following compounds are obtained:

Preparation XV5-[3-[(5-Benzodioxolylsulfonyl)amino]-6-chloro-2-pyridyl]-4-pentynoicacid, methyl ester

Brown solid, yield=92%.

m.p.=133° C.

Preparation XVI5-[3-[(6-Benzothiazolylsulfonyl)amino]-6-chloro-2-pyridyl]-4-pentynoicacid, methyl ester

Yellow solid, yield=49%.

m.p.=137° C.

Preparation XVII2-[[3-(3-Amino-6-chloro-2-pyridyl)-2-propynyl]oxy]propanoic acid, ethylester

By working in a manner similar to that of Preparation V, starting withthe ethyl ester of 2-(2-propynyloxy)propanoic acid, the expected productis obtained in the form of a brown solid (yield=73%).

m.p.=70° C.

Preparation XVIIIN-(6-Chloro-2-iodo-3-pyridyl)-3-methoxybenzenesulfonamide

By working in a manner similar to that of Preparation VII, starting withthe compound according to Preparation I and 3-methoxybenzenesulfonylchloride, the expected product is obtained in the form of a white solid(yield=96%).

m.p.=154° C.

Preparation XIX2-[[3-[3-Amino-6-(trifluoromethyl)-2-pyridyl]-2-propynyl]oxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Preparation V, starting withthe compound according to Preparation IV and the methyl ester of2-methyl-2-(2-propynyloxy)propanoic acid, the expected product isobtained in the form of a yellow oil (yield=56%).

¹H NMR (250 MHz, DMSO-d₆) δ: 7.50 (d, 1H); 7.18 (d, 1H); 6.23 (s, 2H);4.44 (s, 2H); 3.68 (s, 3H); 1.42 (s, 6H).

Preparation XX2-[[3-[3-Amino-6-(trifluoromethyl)-2-pyridyl]-2-propynyl]oxy]propanoicacid, ethyl ester

800 mg (2.78 mM) of the compound according to Preparation IV, 78 mg(0.28 mM) of tricyclohexylphosphine, 20 ml of dimethylformamide, 97 mg(0.14 mM) of dichlorobis(triphenylphosphine)palladium, 26 mg (0.14 mM)of cuprous iodide and 8 ml of t-butylamine are mixed together. 1.09 g (7mM) of the ethyl ester of 2-(2-propynyloxy)propanoic acid are then addedwith stirring, at room temperature, and the reaction mixture is stirredfor 20 hours at 45-50° C. The reaction mixture is then cooled, dilutedwith water and extracted several times with ethyl acetate. The combinedorganic phases are washed with sodium chloride solution, dried overmagnesium sulfate and concentrated under reduced pressure. The crudeproduct obtained is purified by chromatography on silica gel, elutingwith a toluene/ethyl acetate mixture (9/1 and then 8/2; v/v). Theexpected product is thus obtained in the form of an oil (yield: 76%).

¹H NMR (300 MHz, DMSO-d₆) δ: 7.51 (d, 1H); 7.18 (d, 1H); 6.27 (s, 2H);4.58 (d, 1H); 4.48 (d, 1H); 4.23 (q, 1H); 4.12 (q, 2H); 1.31 (d, 3H);1.20 (t, 3H).

Preparation XXI 5-[3-Amino-6-(trifluoromethyl)-2-pyridyl]-4-pentynoicacid, methyl ester

By working in a manner similar to that of Preparation V, starting withthe compound according to Preparation IV and the methyl ester of4-pentynoic acid, the expected product is obtained in the form of anochre-colored solid (yield=81%).

m.p.=90° C.

Preparation XXII 6-[3-Amino-6-(trifluoromethyl)-2-pyridyl]-5-hexynoicacid, methyl ester

By working in a manner similar to that of Preparation XXI, starting withthe methyl ester of 5-hexynoic acid, the expected product is obtained inthe form of a brown solid (yield=94%).

m.p.=49° C.

Preparation XXIII 6-(3-Amino-6-chloro-2-pyridyl)-6-heptynoic acid,methyl ester

By working in a manner similar to that of Preparation V, starting withthe methyl ester of 6-heptynoic acid, the expected product is obtainedin the form of a yellow oil (yield=85%).

¹H NMR (300 MHz, DMSO-d₆) δ: 7.09 (s, 2H); 5.60 (s, 2H); 3.60 (s, 3H);2.50 (m, 2H); 2.37 (t, 2H); 1.63 (m, 4H).

By working in a manner similar to that of Preparation VII, starting withthe compound according to Preparation I and the appropriate sulfonylchlorides, the following aryl or heteroarylsulfonamides are obtained:

Preparation XXIV N-(6-Chloro-2-iodo-3-pyridyl)-4-ethylbenzenesulfonamide

Yellow solid, yield=88%.

m.p.=141° C.

Preparation XXVN-(6-Chloro-2-iodo-3-pyridyl)-4-methoxybenzenesulfonamide

Brown solid, yield=98%.

m.p.=93° C.

Preparation XXVIN-(6-Chloro-2-iodo-3-pyridyl)-2,3-dichlorobenzenesulfonamide

Beige-colored solid, yield=99%.

m.p.>260° C.

Preparation XXVIIN-(6-Chloro-2-iodo-3-pyridyl)-4-(1-methylethyl)benzenesulfonamide

Yellow solid, yield=93%.

m.p.=132° C.

Preparation XXVIIIN-(6-Chloro-2-iodo-3-pyridyl)-1-naphthalenesulfonamide

White solid, yield=54%.

m.p.=135° C.

Preparation XXIX N-(6-Chloro-2-iodo-3-pyridyl)-8-quinolinesulfonamide

Pink solid, yield=14%.

m.p.=199° C.

Preparation XXXN-(6-Chloro-2-iodo-3-pyridyl)-2,5-dimethoxybenzenesulfonamide

Beige-colored solid, yield=99%.

m.p.=147° C.

Preparation XXXIN-(6-Chloro-2-iodo-3-pyridyl)-1,3-benzodioxole-5-sulfonamide

White solid, yield=95%.

m.p.=187° C.

Preparation XXXIIN-(6-Chloro-2-iodo-3-pyridyl)-2,3-dihydro-1,4-benzodioxine-6-sulfonamide

Yellow solid, yield=94%.

m.p.=122° C.

Preparation XXXIIIN-(6-Chloro-2-iodo-3-pyridyl)-2,3-dihydro-5-benzofuransulfonamide

White solid, yield=94%.

m.p.=187° C.

Preparation XXXIVN-(6-Chloro-2-iodo-3-pyridyl)-3,5-dimethylbenzenesulfonamide

Beige-colored solid, yield=99%.

m.p.=138° C.

Preparation XXXVN-(6-Chloro-2-iodo-3-pyridyl)-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-7-sulfonamide

White solid, yield=99%.

m.p.=139° C.

Preparation XXXVI N-(2-Bromo-6-methyl-3-pyridyl)benzenesulfonamide

By working in a manner similar to that of Preparation VII, starting with3-amino-2-bromo-6-methylpyridine, the expected product is obtained inthe form of a beige-colored solid (yield=95%).

¹H NMR (250 MHz, DMSO-d₆) δ: 10.05 (s, 1H); 7.70 (m, 3H); 7.61 (d, 2H);7.47 (d, 1H); 7.25 (d, 1H); 2.39 (s, 3H).

Preparation XXXVII 3-Amino-2-bromo-6-methoxypyridine

A mixture of 1.83 g (14.7 mM) of 5-amino-2-methoxypyridine and 1.21 g(14.7 mM) of sodium acetate in 12 ml of acetic acid is prepared and 0.75ml (14.7 mM) of bromine is added gently, with stirring and whilemaintaining at room temperature. The reaction mixture is kept stirringfor 30 minutes, at room temperature, and 200 ml of saturated sodiumthiosulfate solution are then added. The aqueous phase obtained isextracted twice with ethyl acetate. The combined organic phases aredried over magnesium sulfate and concentrated under reduced pressure. 3g of the expected compound are obtained in the form of a violet-coloredsolid (quantitative yield).

¹H NMR (250 MHz, DMSO-d₆) δ: 7.18 (d, 1H); 6.64 (d, 1H); 4.91 (s, 2H);3.71 (s, 3H).

Preparation XXXVIII (2-Bromo-6-methoxy-3-pyridyl)benzenesulfonamide

By working in a manner similar to that of Preparation VII, starting with3-amino-2-bromo-6-methoxypyridine, the expected product is obtained inthe form of a brown solid (yield=50%).

¹H NMR (250 MHz, DMSO-d₆) δ: 9.92 (s, 1H); 7.67 (m, 3H); 7.57 (m, 2H);7.45 (d, 1H); 6.84 (d, 1H); 3.80 (s, 3H).

Preparation XXXIX 3-Amino-2-iodo-6-methoxypyridine

By working in a manner similar to that of Preparation IV, starting with5-amino-2-methoxypyridine, the expected product is obtained in the formof a brown oil (yield=6%).

¹H NMR (300 MHz, DMSO-d₆) δ: 7.08 (d, 1H); 6.62 (d, 1H); 4.81 (s, 2H);3.71 (s, 3H).

Preparation XL (2-Iodo-6-methoxy-3-pyridyl)benzenesulfonamide

By working in a manner similar to that of Preparation VII, starting with3-amino-2-iodo-6-methoxypyridine, the expected product is obtained inthe form of a brown solid (yield=91%).

¹H NMR (250 MHz, DMSO-d₆) δ: 9.84 (s, 1H); 7.65 (m, 5H); 7.17 (d, 1H);6.77 (d, 1H); 3.79 (s, 3H).

Preparation XLIN-(2-Bromo-6-methyl-3-pyridyl)-6-benzothiazolesulfonamide

By working in a manner similar to that of Preparation VII, starting with3-amino-2-bromo-6-methylpyridine and 6-benzothiazolesulfonyl chloride,the expected product is obtained in the form of a beige-colored paste(yield=35%).

¹H NMR (250 MHz, DMSO-d₆) δ: 10.20 (s, 1H); 9.63 (s, 1H); 8.61 (d, 1H);8.25 (d, 1H); 7.85 (dd, 1H); 7.49 (d, 1H); 7.26 (d, 1H); 2.39 (s, 3H).

Preparation XLII N-(6-Chloro-2-iodo-3-pyridyl)-3-pyridinesulfonamide

By working in a manner similar to that of Preparation XVIII, startingwith 3-pyridinesulfonyl chloride, the expected product is obtained inthe form of a pasty compound, which is used without further purificationfor the preparation of the compound according to Example 252.

Preparation XLIII N-(6-Chloro-2-iodo-3-pyridyl)-6-quinolinesulfonamide

By working in a manner similar to that of Preparation XVIII startingwith 6-quinolinesulfonyl chloride, the expected product is obtained inthe form of a white solid (yield=99%)

m.p.>250° C.

Preparation XLIVN-(2-Iodo-6-chloro-3-pyridyl)-6-benzothiazolesulfonamide

By working in a manner similar to that of Example 50, starting with3-amino-2-iodo-6-chloropyridine and 6-benzothiazolesulfonyl chloride,the expected product is obtained in the form of an orange-colored solid(yield=33%).

m.p.=191° C.

Preparation XLV 5-(Trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with themethyl ester according to Preparation XXII, the expected product isobtained in the form of a beige-colored solid (yield=66%).

m.p.=137° C.

Preparation XLVI6-[6-Chloro-3-[[(4-fluoro-3-nitrophenyl)sulfonyl]amino]-2-pyridyl]-5-hexynoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting with4-fluoro-3-nitrobenzenesulfonyl chloride, the expected product isobtained in the form of a yellow oil (yield=31%).

¹H NMR (300 MHz, DMSO-d₆) δ: 10.63 (s, 1H); 8.41 (dd, 1H); 8.06 (m, 1H);7.75 (m, 2H); 7.46 (d, 1H); 3.61 (s, 3H); 2.39 (m, 4H); 1.72 (quint.,2H).

Preparation XLVII6-[3-[[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]amino]-6-chloro-2-pyridyl]-5-hexynoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting with2,1,3-benzothiadiazole-4-sulfonyl chloride, the expected compound isobtained in the form of a beige-colored solid (yield=64%).

¹H NMR (250 MHz, DMSO-d₆) δ: 10.36 (s, 1H); 8.40 (d, 1H); 8.18 (d, 1H);7.84 (m, 2H); 7.48 (d, 1H); 3.62 (s, 3H); 2.26 (t, 2H); 2.01 (t, 2H);1.47 (quint., 2H).

Example 52-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Example 1, starting with theethyl ester of 2-(2-propynyloxy)propanoic acid, the expected compound isobtained in the form of a yellow oil (yield=62%).

¹H NMR (300 MHz, DMSO-d₆) δ: 1.18 (t, 3H); 1.31 (d, 3H); 4.12 (q, 2H);4.24 (q, 1H); 4.92 (d, 1H); 5.05 (d, 1H); 6.95 (s, 1H); 7.43 (d, 1H);7.60 t, 2H); 7.74 (t, 1H); 8.02 (d, 2H); 8.42 (d, 1H).

Example 62-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 5, the expected compound is obtainedin the form of a white solid (yield=57%).

m.p.=153-155° C.

Example 72-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 1, starting with themethyl ester of 2-methyl-2-(2-propynyloxy)propanoic acid, the expectedcompound is obtained in the form of a white solid (yield=20%).

m.p.=84-87° C.

Example 82-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 7, the expected compound is obtainedin the form of a white solid (yield=57%).

m.p.=183-185° C.

Example 95-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid,methyl ester

By working in a manner similar to that of Example 1, starting with themethyl ester of 5-hexynoic acid, the expected compound is obtained inthe form of a yellow solid (yield=38%).

m.p.=85-90° C.

Example 105-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 9, the expected compound is obtainedin the form of a beige-colored solid (yield=38%).

m.p.=160-164° C.

Example 113-(1-Benzenesulfonyl-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl)-2,2-dimethylpropanoicacid, methyl ester

By working in a manner similar to that of Example 1, starting with themethyl ester of 2,2-dimethyl-4-pentynoic acid, the expected compound isobtained in the form of a yellow oil (yield=82%).

¹H NMR (300 MHz, DMSO-d₆) δ: 1.22 (s, 6H); 3.41 (s, 2H); 3.62 (s, 3H);6.58 (s, 1H); 7.40 (d, 1H); 7.59 (t, 2H); 7.72 (t, 1H); 7.82 (d, 2H);8.42 (d, 1H).

Example 123-(1-Benzenesulfonyl-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl)-2,2-dimethylpropanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 11, the expected compound isobtained in the form of a white solid (yield=18%).

m.p.=208-211° C.

Example 132-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Example 1, starting with thecompound according to Preparation VII and the ethyl ester of2-(2-propynyloxy)propanoic acid, the expected compound is obtained inthe form of a colorless oil (yield=63%).

¹H NMR (300 MHz, DMSO-d₆) δ: 1.17 (t, 3H); 1.31 (d, 3H); 4.11 (q, 2H);4.23 (q, 1H); 4.97 (d, 1H); 5.10 (d, 1H); 7.12 (s, 1H); 7.61 (t, 2H);7.75 (t, 1H); 7.80 (d, 1H); 8.06 (d, 2H); 8.63 (d, 1H).

Example 142-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 13, the expected compound isobtained in the form of a white solid (yield=56%).

m.p.=53-57° C.

Example 152-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 13, starting with thecompound according to Preparation VII and the methyl ester of2-methyl-2-(2-propynyloxy)propanoic acid, the expected compound isobtained in the form of a yellow oil (yield=30%).

¹H NMR (300 MHz, DMSO-d₆) δ: 1.44 (s, 6H); 3.65 (s, 3H); 4.93 (s, 2H);7.10 (s, 1H); 7.63 (t, 2H); 7.76 (t, 1H); 7.83 (d, 1H); 8.05 (d, 2H);8.64 (d, 1H).

Example 162-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 15, the expected compound isobtained in the form of a beige-colored solid (yield=45%).

m.p.=122-125° C.

Example 171-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 13, starting with themethyl ester of 4-pentynoic acid, the expected compound is obtained inthe form of a beige-colored solid (yield=91%).

m.p.=119° C.

Example 181-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 17, the expected compound isobtained in the form of a white solid (yield=53%).

m.p.=180° C.

Example 191-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 13, starting with themethyl ester of 5-hexynoic acid, the expected compound is obtained inthe form of a beige-colored solid (yield=88%).

m.p.=95° C.

Example 201-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 19, the expected compound isobtained in the form of a white solid (yield=58%).

m.p.=168° C.

Example 211-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation X, the expected compound is obtainedin the form of a yellow solid (yield=63%).

m.p.=85-90° C.

Example 221-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 21, the expected product isobtained in the form of a white solid (yield=82%).

m.p.>250° C.

Example 231-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation IX, the expected compound is obtainedin the form of a yellow solid (yield=74%).

m.p.=120° C.

Example 241-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 23, the expected product isobtained in the form of a beige-colored solid (yield=95%).

m.p.=160° C.

Example 255-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XI, the expected compound is obtainedin the form of a brown solid (yield=99%).

m.p.=138° C.

Example 265-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 25, the expected product isobtained in the form of a beige-colored solid (yield=88%).

m.p.=200° C.

Example 275-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XII, the expected compound is obtainedin the form of a beige-colored solid (yield=94%).

m.p.=102° C.

Example 285-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 27, the expected product isobtained in the form of a white solid (yield=95%).

m.p.=227-231° C.

Example 295-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XIII, the expected compound isobtained in the form of a yellow oil (yield=86%).

¹H NMR (300 MHz, DMSO-d₆) δ: 1.83 (quint., 2H); 2.34 (t, 2H); 2.88 (t,2H); 3.52 (s, 3H); 6.83 (s, 1H); 7.39 (d, 1H); 7.71 (m, 4H); 8.14 (m,1H); 8.30 (m, 1H); 8.37 (m, 2H).

Example 305-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 29, the expected product isobtained in the form of a white solid (yield=96%).

m.p.=202-206° C.

Example 315-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XIV, the expected compound is obtainedin the form of a white solid (yield=78%).

m.p.=106-110° C.

Example 325-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 31, the expected product isobtained in the form of a white solid (yield=98%).

m.p.=180-183° C.

Example 331-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XV, the expected compound is obtainedin the form of a yellow oil (yield=76%).

¹H NMR (300 MHz, DMSO-d₆) δ: 2.84 (t, 2H); 3.31 (t, 2H); 3.47 (t, 2H);3.62 (s, 3H); 6.16 (s, 2H); 6.72 (s, 1H); 7.09 (d, 1H); 7.37 (d, 1H);7.38 (s, 1H); 7.51 (dd, 1H); 8.40 (s, 1H).

Example 341-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 33, the expected product isobtained in the form of a brown solid (yield=98%).

m.p.=186° C.

Example 351-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with thecompound according to Preparation XVI, the expected compound is obtainedin the form of a white solid (yield=57%).

m.p.=146° C.

Example 361-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with thecompound obtained according to Example 35, the expected product isobtained in the form of a white solid (yield=90%).

m.p.=248° C.

Example 375-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid,sodium salt

1.46 g (4 mM) of the acid obtained according to Example 2 are mixed in12 ml of tetrahydrofuran and 8 ml (4 mM) of a 0.5 N solution of sodiumhydroxide in water are added. The reaction medium is stirred for 2 hoursat room temperature and then concentrated under reduced pressure. Theoily residue is triturated from methanol and the white precipitateformed is separated out by filtration and dried under vacuum. Theexpected salt is obtained in the form of a pulverulent white solid(yield=98%).

m.p.=200° C.

Example 382-[[1-(2,1,3-Benzothiadiazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Preparation VI, starting withthe ester according to Preparation XVII and2,1,3-benzothiadiazole-5-sulfonyl chloride, the expected compound isobtained in the form of an orange-colored solid (yield=46%).

m.p.=77-79° C.

Example 392-[[1-(2,1,3-Benzothiadiazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 38, the expected compound isobtained in the form of a white solid (yield=16%).

m.p.=192-194° C.

Example 402-[[5-Chloro-1-[(2-methyl-7-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Preparation VI, starting withthe ester according to Preparation XVII and2-methyl-7-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a colorless oil (yield=50%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.32 (d, 1H); 8.27 (d, 1H); 7.94 (d, 1H);7.67 (t, 1H); 7.43 (d, 1H); 7.00 (s, 1H); 5.02 (d, 1H); 4.88 (d, 1H);4.13 (q, 1H); 4.07 (q, 2H); 2.85 (s, 3H); 1.15 (m, 6H).

Example 412-[[5-Chloro-1-[(2-methyl-7-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 40, the expected compound isobtained in the form of a white solid (yield=28%).

m.p.=203-205° C.

Example 422-[[5-Chloro-1-[(3-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 1, starting with thecompound according to Preparation XVIII and the methyl ester of2-methyl-2-(2-propynyloxy)propanoic acid, the expected compound isobtained in the form of a white solid (yield=33%).

m.p.=153° C.

Example 432-[[5-Chloro-1-[(3-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

A solution of 186 mg (0.41 mM) of the ester obtained according toExample 42 in 7.5 ml of acetic acid is prepared and 0.75 ml ofconcentrated hydrochloric acid is added, with stirring and at roomtemperature. The reaction medium is maintained under gentle reflux for18 hours and then concentrated under reduced pressure. The evaporationresidue is taken up in water and extracted with dichloromethane. Theorganic phase is washed with water, dried over magnesium sulfate andconcentrated under reduced pressure. The crude product is purified bychromatography on silica gel, eluting with a dichloromethane/methanolmixture (gradient from 99/1 to 90/10, v/v). The expected acid is thusobtained in the form of a beige-colored solid (yield=70%).

m.p.=130° C.

Example 442-[[1-[(2-Acetylamino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Preparation VI, starting withthe ester according to Preparation XVII and2-acetylamino-6-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=25%).

m.p.=100-102° C.

Example 452-[[1-[(2-Acetylamino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo-[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 44, the expected compound isobtained in the form of a white solid (yield=25%).

m.p.=257-260° C.

Example 462-[[1-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Preparation VI, starting withthe ester according to Preparation XVII and2-amino-6-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=25%).

m.p.=86-88° C.

Example 472-[[1-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 46, the expected compound isobtained in the form of a white solid (yield=65%).

m.p.=218-220° C.

Example 482-[[1-(6-Benzothiazolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation XIX and 6-benzothiazolesulfonylchloride, the expected compound is obtained in the form of a white solid(yield=13%).

m.p.=124-127° C.

Example 492-[[1-(6-Benzothiazolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 48, the expected compound isobtained in the form of a white solid (yield=16%).

m.p.=180-182° C.

Example 502-[[1-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid, ethyl ester

A solution of 350 mg (1.24 mM) of the ester according to PreparationXVII in 8 ml of pyridine is prepared and 550 mg (2.35 mM) of6-benzothiazolesulfonyl chloride are added, with stirring and at 0° C.The reaction medium is stirred at room temperature for 24 hours and thendiluted with ethyl acetate. This organic phase is washed with 2 Nhydrochloric acid solution and then with water, dried over magnesiumsulfate and concentrated under reduced pressure. The oil obtained istaken up in 10 ml of THF and 2.6 ml (2.6 mM) of tetrabutylammoniumfluoride as a 1 M solution in THF are gradually added to this solutioncooled to 0° C. The reaction mixture is stirred for 24 hours at 4° C.,and then diluted in DCM. The organic phase obtained is washed with Nhydrochloric acid solution, and then with water, dried over magnesiumsulfate and concentrated under reduced pressure. The crude product ispurified by chromatography on silica gel, eluting with a toluene/ethylacetate mixture (95/5 and then 9/1; v/v). The expected product is thusobtained in the form of a yellow oil (yield=31%).

¹H NMR (250 MHz, DMSO-d₆) δ: 9.68 (s, 1H); 9.11 (d, 1H); 8.50 (d, 1H);8.23 (d, 1H); 8.10 (dd, 1H); 7.43 (d, 1H); 6.96 (s, 1H); 5.08 (d, 1H);4.96 (d, 1H); 4.25 (q, 1H); 4.12 (q, 2H); 1.28 (d, 3H); 1.19 (t, 3H).

Example 512-[[1-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 50, the expected compound isobtained in the form of a white solid (yield=40%).

m.p.=179° C.

Example 522-[[1-(6-Benzothiazolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

A solution of 140 mg (0.443 mM) of the compound according to PreparationXX in 2 ml of pyridine is prepared and 228 mg (0.98 mM) of6-benzothiazolesulfonyl chloride are added. The reaction mixture isstirred at room temperature for 48 hours and then diluted with ethylacetate. The organic phase obtained is washed successively with water,with N hydrochloric acid, again with water, with sodium bicarbonatesolution and finally with sodium chloride solution. After drying overmagnesium sulfate and concentrating, 242 mg of the ethyl ester of2-[[3-[3-(6-benzothiazolylsulfonylamino)-6-(trifluoromethyl)-2-pyridyl]-2-propynyl]oxy]-propanoicacid are obtained, which product is taken up in 5 ml of DCM in a reactortube adapted for heating by microwave. 100 mg (0.5 mM) of copper acetatemonohydrate are added and this mixture is heated at 150° C. for 15minutes. The reaction medium is cooled, filtered and concentrated underreduced pressure. After purification by chromatography on a column ofsilica, eluting with a toluene/ethyl acetate mixture (9/1; v/v), theexpected compound is obtained in the form of a beige-colored solid(yield=42%).

m.p.=96° C.

Example 532-[[1-(6-Benzothiazolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 52, the expected compound isobtained in the form of a beige-colored solid (yield=50%).

m.p.=124° C.

Example 545-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and 2,5-dimethoxybenzenesulfonylchloride, the expected compound is obtained in the form of abeige-colored solid (yield=77%).

m.p.=127° C.

Example 555-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 54, the expected compound isobtained in the form of a white solid (yield=71%).

m.p.=204-209° C.

Example 561-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with theester according to Preparation VIII and 2-amino-6-benzothiazolesulfonylchloride, the expected compound is obtained in the form of a yellowsolid (yield=38%).

m.p.=205-215° C.

Example 571-[(2-Amino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 56, the expected compound isobtained in the form of a beige-colored solid (yield=57%).

m.p.>260° C.

Example 585-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and 3,5-dimethylbenzenesulfonylchloride, the expected compound is obtained in the form of a white solid(yield=86%).

m.p.=182-185° C.

Example 595-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 58, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=181-186° C.

Example 605-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and3,4-dihydro-4-methyl-2H-1,4-benzoxazine-7-sulfonyl chloride, theexpected compound is obtained in the form of a yellow oil (yield=87%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.43 (d, 1H); 7.37 (d, 1H); 7.07 (dd, 1H);6.94 (d, 1H); 6.81 (d, 1H); 6.69 (s, 1H); 4.25 (m, 2H); 3.62 (s, 3H);3.26 (m, 4H); 2.86 (m, 2H); 2.82 (s, 3H).

Example 615-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 60, the expected compound isobtained in the form of a white solid (yield=98%).

m.p.=175-185° C.

Example 625-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and 8-quinolinesulfonyl chloride,the expected compound is obtained in the form of a white solid(yield=59%).

m.p.=120° C.

Example 635-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 62, the expected compound isobtained in the form of a white solid (yield=98%).

m.p.=183° C.

Example 645-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and 1-naphthalenesulfonylchloride, the expected compound is obtained in the form of a yellow oil(yield=66%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.34 (m, 3H); 8.15 (m, 1H); 7.69 (m, 4H);7.39 (d, 1H); 6.81 (s, 1H); 3.56 (s, 3H); 3.12 (t, 2H); 2.74 (t, 2H).

Example 655-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 64, the expected compound isobtained in the form of a white solid (yield=86%).

m.p.=93° C.

Example 661-[(1-Acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-5-chloro-1H-pyrrolo-[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and1-acetyl-2,3-dihydro-1H-indole-5-sulfonyl chloride, the expectedcompound is obtained in the form of a brown solid (yield=93%).

m.p.=66° C.

Example 671-[(1-Acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-5-chloro-1H-pyrrolo-[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 66, the expected compound isobtained in the form of a yellow solid (yield=37%).

m.p.=216° C.

Example 685-Chloro-1-[3-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation VIII and3-(trifluoromethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of an orange-colored solid (yield=71%).

m.p.=102° C.

Example 695-Chloro-1-[3-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 68, the expected compound isobtained in the form of a yellow solid (yield=9%).

m.p.=146° C.

Example 701-[(3,5-Dimethylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation XXI and 3,5-dimethylbenzenesulfonylchloride, the expected compound is obtained in the form of abeige-colored solid (yield=51%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.60 (d, 1H); 7.79 (d, 1H); 7.57 (s, 2H);7.39 (s, 1H); 6.90 (s, 1H); 3.63 (s, 3H); 3.33 (t, 2H); 2.87 (t, 2H);2.31 (s, 6H).

Example 711-[(3,5-Dimethylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 70, the expected compound isobtained in the form of a white solid (yield=91%).

m.p.=185-189° C.

Example 721-(8-Quinolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation XXI and 8-quinolinesulfonyl chloride,the expected compound is obtained in the form of a white solid(yield=51%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.72 (m, 2H); 8.45 (m, 3H); 7.88 (t, 1H);7.72 (d, 1H); 7.62 (dd, 1H); 6.76 (s, 1H); 3.60 (s, 3H); 3.54 (t, 2H);2.88 (t, 2H)

Example 731-(8-Quinolylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 72, the expected compound isobtained in the form of a white solid (yield=56%).

m.p.=216-217° C.

Example 741-(1-Naphthalenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation XXI and 1-naphthalenesulfonylchloride, the expected compound is obtained in the form of abeige-colored solid (yield=63%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.56 (d, 1H); 8.36 (m, 2H); 8.17 (m, 1H);7.72 (m, 5H); 6.98 (s, 1H); 3.56 (s, 3H); 3.15 (t, 2H); 2.77 (t, 2H).

Example 751-(1-Naphthalenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 74, the expected compound isobtained in the form of a white solid (yield=42%).

m.p.=116-117° C.

Example 765-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation V and 8-quinolinesulfonyl chloride,the expected compound is obtained in the form of a white solid(yield=25%).

m.p.=64° C.

Example 775-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 76, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=186-189° C.

Example 785-Chloro-1-[(2,2-difluoro-1,3-benzodioxol-5-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,2-difluoro-1,3-benzodioxole-5-sulfonyl chloride, the expected compoundis obtained in the form of a colorless oil (yield=95%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.43 (d, 1H); 8.09 (d, 1H); 7.83 (dd, 1H);7.60 (d, 1H); 7.38 (d, 1H); 6.77 (s, 1H); 3.59 (s, 3H); 3.07 (t, 2H);2.45 (t, 2H); 1.97 (m, 2H).

Example 795-Chloro-1-[(2,2-difluoro-1,3-benzodioxol-5-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 78, the expected compound isobtained in the form of a white solid (yield=78%).

m.p.=216° C.

Example 805-Chloro-1-[(2-methyl-5-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-methyl-5-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a beige-colored solid (yield=79%).

m.p.=114° C.

Example 815-Chloro-1-[(2-methyl-5-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 80, the expected compound isobtained in the form of a beige-colored solid (yield=98%).

m.p.=173° C.

Example 825-Chloro-1-[(2-methyl-6-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-methyl-6-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a beige-colored solid (yield=69%).

m.p.=117° C.

Example 835-Chloro-1-[(2-methyl-6-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 82, the expected compound isobtained in the form of a yellow solid (yield=99%).

m.p.=184° C.

Example 845-Chloro-1-[(2-methyl-7-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and2-methyl-7-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=48%).

m.p.=138° C.

Example 855-Chloro-1-[(2-methyl-7-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 84, the expected compound isobtained in the form of a beige-colored solid (yield=90%).

m.p.=225° C.

Example 865-Chloro-1-[(2,3-dihydro-5-benzofuryl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,3-dihydro-5-benzofuransulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=82%).

m.p.=201° C.

Example 875-chloro-1-[(2,3-dihydro-5-benzofuryl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 86, the expected compound isobtained in the form of a white solid (yield=98%).

m.p.=225° C.

Example 885-Chloro-1-[(3,5-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3,5-dichlorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=66%).

m.p.=112-114° C.

Example 895-Chloro-1-[(3,5-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 88, the expected compound isobtained in the form of a white solid (yield=28%).

m.p.=164-165° C.

Example 901-[(2-Acetylamino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-acetylamino-6-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=35%).

m.p.=274° C.

Example 911-[(2-Acetylamino-6-benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 90, the expected compound isobtained in the form of a white solid (yield=87%).

m.p.=270° C.

Example 921-[(2-Amino-6-benzoxazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-amino-6-benzoxazolesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=35%).

m.p.=241° C.

Example 931-[(2-Amino-6-benzoxazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 92, the expected compound isobtained in the form of a white solid (yield=96%).

m.p.=273° C.

Example 945-Chloro-1-[(2-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-fluorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a brown solid (yield=87%).

m.p.=83° C.

Example 955-Chloro-1-[(2-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 94, the expected compound isobtained in the form of a beige-colored solid (yield=92%).

m.p.=176° C.

Example 965-Chloro-1-[[2-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and2-(trifluoromethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=39%).

m.p.=127° C.

Example 975-Chloro-1-[[2-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 96, the expected compound isobtained in the form of a yellow solid (yield=89%).

m.p.=171° C.

Example 981-([1,1′-Biphenyl]-3-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and [1,1′-biphenyl]-3-sulfonylchloride, the expected compound is obtained in the form of a white solid(yield=68%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.49 (d, 1H); 8.03 (m, 2H); 7.78 (d, 1H);7.66 (m, 3H); 7.47 (m, 3H); 7.39 (d, 1H); 6.79 (s, 1H); 3.55 (s, 3H);3.11 (t, 2H); 2.44 (t, 2H); 2.01 (m, 2H).

Example 991-([1,1′-Biphenyl]-3-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 98, the expected compound isobtained in the form of a white solid (yield=23%).

m.p.=147-149° C.

Example 1005-Chloro-1-[(4-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and 4-fluorobenzenesulfonylchloride, the expected compound is obtained in the form of a yellowsolid (yield=29%).

m.p.=119° C.

Example 1015-Chloro-1-[(4-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 100, the expected compound isobtained in the form of a beige-colored solid (yield=66%).

m.p.=180° C.

Example 1025-Chloro-1-[(3-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-fluorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a brown solid (yield=76%).

m.p.=104° C.

Example 1035-Chloro-1-[(3-fluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 102, the expected compound isobtained in the form of a beige-colored solid (yield=75%).

m.p.=163° C.

Example 1041-[(1-Acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with1-acetyl-2,3-dihydro-1H-indole-5-sulfonyl chloride, the expectedcompound is obtained in the form of a beige-colored solid (yield=91%).

m.p.=123° C.

Example 1051-[(1-Acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 104, the expected compound isobtained in the form of a beige-colored solid (yield=54%).

m.p.=226° C.

Example 1065-Chloro-1-[(6-chloroimidazo[2,1-b]thiazol-5-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with6-chloroimidazo[2,1-b]thiazole-5-sulfonyl chloride, the expectedcompound is obtained in the form of a colorless oil (yield=70%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.55 (s, 1H); 8.43 (d, 1H); 7.95 (m, 5H);7.39 (d, 1H); 6.78 (s, 1H); 3.58 (s, 3H); 3.07 (t, 2H); 2.44 (t, 2H);1.97 (m, 2H).

Example 1075-Chloro-1-[(6-chloroimidazo[2,1-b]thiazol-5-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 106, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=186° C.

Example 1085-Chloro-1-[[4-(1H-pyrazol-1-yl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and4-(1H-pyrazol-1-yl)benzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=10%).

m.p.=122-124° C.

Example 1095-Chloro-1-[[4-(1H-pyrazol-1-yl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 108, the expected compound isobtained in the form of a white solid (yield=58%).

m.p.=196-207° C.

Example 1105-Chloro-1-[[3-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and3-(trifluoromethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a yellow solid (yield=11%).

m.p.=97° C.

Example 1115-Chloro-1-[[3-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 110, the expected compound isobtained in the form of a yellow solid (yield=41%).

m.p.=188° C.

Example 1125-Chloro-1-[[4-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and4-(trifluoromethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a beige-colored solid (yield=27%).

m.p.=99° C.

Example 1135-chloro-1-[[4-(trifluoromethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 112, the expected compound isobtained in the form of a white solid (yield=27%).

m.p.=185° C.

Example 1145-Chloro-1-[[4-(5-oxazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(5-oxazolyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a colorless oil (yield=50%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.55 (s, 1H); 8.43 (d, 1H); 7.95 (m, 5H);7.39 (d, 1H); 6.78 (s, 1H); 3.58 (s, 3H); 3.07 (t, 2H); 2.44 (t, 2H);1.97 (m, 2H).

Example 1155-Chloro-1-[[4-(5-oxazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 114, the expected compound isobtained in the form of a white solid (yield=27%).

m.p.=169-176° C.

Example 1161-[[3,5-Bis(trifluoromethyl)phenyl]sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3,5-bis(trifluoromethyl)benzenesulfonyl chloride, the expected compoundis obtained in the form of a white solid (yield=62%).

m.p.=134-144° C.

Example 1171-[[3,5-Bis(trifluoromethyl)phenyl]sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 116, the expected compound isobtained in the form of a beige-colored solid (yield=6%).

m.p.=155-164° C.

Example 1185-Chloro-1-[(4-chloro-3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-chloro-3-methylbenzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=78%).

m.p.=111-114° C.

Example 1195-Chloro-1-[(4-chloro-3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 118, the expected compound isobtained in the form of a white solid (yield=42%).

m.p.=175-183° C.

Example 1201-([1,1′-Biphenyl]-4-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with[1,1′-biphenyl]-4-sulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=85%).

m.p.=122-124° C.

Example 1211-([1,1′-Biphenyl]-4-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 120, the expected compound isobtained in the form of a white solid (yield=55%).

m.p.=186-190° C.

Example 1225-Chloro-1-[(3,4-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3,4-difluorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=61%).

m.p.=96-98° C.

Example 1235-Chloro-1-[(3,4-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 122, the expected compound isobtained in the form of a beige-colored solid (yield=59%).

m.p.=180-190° C.

Example 1245-Chloro-1-[3-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-(trifluoromethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of a brown oil (yield=84%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.44 (d, 1H); 7.89 (m, 2H); 7.77 (m, 2H);7.39 (d, 1H); 6.80 (s, 1H); 3.58 (s, 3H); 3.06 (t, 2H); 2.44 (t, 2H);1.96 (quint., 2H).

Example 1255-Chloro-1-[3-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 124, the expected compound isobtained in the form of a beige-colored solid (yield=37%).

m.p.=176° C.

Example 1261-(1,2,3-Benzothiadiazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and1,2,3-benzothiadiazole-5-sulfonyl chloride, the expected compound isobtained in the form of a beige-colored solid (yield=9%).

m.p.=219° C.

Example 1271-(1,2,3-Benzothiadiazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 126, the expected compound isobtained in the form of a white solid (yield=58%).

m.p.=227° C.

Example 1285-Chloro-1-[4-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(trifluoromethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=52%).

m.p.=109° C.

Example 1295-Chloro-1-[4-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 128, the expected compound isobtained in the form of a white solid (yield=88%).

m.p.=168° C.

Example 1305-Chloro-1-[(3-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-chlorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a white solid (yield=14%).

m.p.=107° C.

Example 1315-Chloro-1-[(3-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 130, the expected compound isobtained in the form of a beige-colored solid (yield=83%).

m.p.=174° C.

Example 1325-Chloro-1-[(4-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-chlorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a beige-colored solid (yield=35%).

m.p.=108° C.

Example 1335-Chloro-1-[(4-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 132, the expected compound isobtained in the form of a beige-colored solid (yield=81%).

m.p.=174° C.

Example 1345-Chloro-1-[(3-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-methoxybenzenesulfonyl chloride, the expected compound is obtained inthe form of a yellow solid (yield=45%).

m.p.=90° C.

Example 1355-Chloro-1-[(3-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 134, the expected compound isobtained in the form of a beige-colored solid (yield=94%).

m.p.=139° C.

Example 1365-Chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-methoxybenzenesulfonyl chloride, the expected compound is obtained inthe form of a beige-colored solid (yield=66%).

m.p.=96° C.

Example 1375-Chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 136, the expected compound isobtained in the form of a white solid (yield=78%).

m.p.=189° C.

Example 1385-Chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-methylbenzenesulfonyl chloride, the expected compound is obtained inthe form of a gray solid (yield=37%).

m.p.=106° C.

Example 1395-Chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 138, the expected compound isobtained in the form of a white solid (yield=87%).

m.p.=172° C.

Example 1405-Chloro-1-[[4-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(1-methylethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=51%).

m.p.=75° C.

Example 1415-Chloro-1-[[4-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 140, the expected compound isobtained in the form of a white solid (yield=88%).

m.p.=155° C.

Example 1425-Chloro-1-[[3-(2-methyl-4-pyrimidinyl)phenyl]sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-(2-methyl-4-pyrimidinyl)benzenesulfonyl chloride, the expectedcompound is obtained in the form of a yellow solid (yield=78%).

m.p.=140-144° C.

Example 1435-Chloro-1-[[3-(2-methyl-4-pyrimidinyl)phenyl]sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 142, the expected compound isobtained in the form of a white solid (yield=38%).

m.p.=178-188° C.

Example 1441-(1,2-Benzisoxazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and 1,2-benzisoxazole-5-sulfonylchloride, the expected compound is obtained in the form of abeige-colored solid (yield=7%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.42 (d, 1H); 8.32 (d, 1H); 7.98 (dd, 1H);7.36 (d, 1H); 7.10 (d, 1H); 6.75 (s, 1H); 3.58 (s, 3H); 3.05 (t, 2H);2.45 (t, 2H); 1.95 (quint., 2H).

Example 1451-(1,2-Benzisoxazol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 144, the expected compound isobtained in the form of a yellow solid (yield=33%).

m.p.=226° C.

Example 1465-Chloro-1-[2-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and2-(trifluoromethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of a pasty white solid.

Example 1475-Chloro-1-[2-(trifluoromethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 146, the expected compound isobtained in the form of a white solid (yield=50%).

m.p.=138° C.

Example 1485-Chloro-1-[(3,5-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3,5-difluorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a beige-colored solid (yield=83%).

m.p.=90° C.

Example 1495-Chloro-1-[(3,4-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 148, the expected compound isobtained in the form of a gray solid (yield=24%).

¹H NMR (300 MHz, DMSO-d₆) δ: 12.11 (s, 1H); 8.44 (d, 1H); 7.75 (m, 3H);7.38 (d, 1H); 6.80 (s, 1H); 3.08 (t, 2H); 2.37 (m, 2H); 1.94 (m, 2H).

Example 1505-Chloro-1-[(2,5-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,5-dichlorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a beige-colored solid (yield=65%).

m.p.=95-105° C.

Example 1515-Chloro-1-[(2,5-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 150, the expected compound isobtained in the form of a gray solid (yield=43%).

m.p.=86-89° C.

Example 1525-Chloro-1-[(2-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-chlorobenzenesulfonyl chloride, the expected compound is obtained,which is reacted directly to obtain the acid.

Example 1535-Chloro-1-[(2-chlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 152, the expected compound isobtained in the form of a beige-colored solid (yield=48%).

m.p.=139° C.

Example 1545-Chloro-1-[(2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-methylbenzenesulfonyl chloride, the expected compound is obtained,which is reacted directly to obtain the corresponding acid.

Example 1555-Chloro-1-[(2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 154, the expected compound isobtained in the form of a white solid (yield=66%).

m.p.=161° C.

Example 1565-Chloro-1-[(3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-methylbenzenesulfonyl chloride, the expected compound is obtained,which is reacted directly to obtain the corresponding acid.

Example 1575-Chloro-1-[(3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 156, the expected compound isobtained in the form of a white solid (yield=38%).

m.p.=165° C.

Example 1585-Chloro-1-[(2,6-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,6-difluorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=76%).

m.p.=107-109° C.

Example 1595-Chloro-1-[(2,6-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 158, the expected compound isobtained in the form of a white solid (yield=38%).

m.p.=192-195° C.

Example 1605-Chloro-1-[(2,4,6-trifluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,4,6-trifluorobenzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=71%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.20 (d, 1H); 7.56 (m, 2H); 7.41 (d, 1H);6.84 (s, 1H); 3.57 (s, 3H); 2.94 (t, 2H); 2.41 (t, 2H); 1.94 (quint.,2H).

Example 1615-Chloro-1-[(2,4,6-trifluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 160, the expected compound isobtained in the form of a beige-colored solid (yield=27%).

m.p.=135-150° C.

Example 1625-Chloro-1-[(2,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,5-dimethylbenzenesulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=87%).

m.p.=92-103° C.

Example 1635-Chloro-1-[(2,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 162, the expected compound isobtained in the form of a yellow solid (yield=72%).

m.p.=106-117° C.

Example 1645-Chloro-1-[(3,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3,5-dimethoxybenzenesulfonyl chloride, the expected compound is obtainedin the form of a beige-colored solid (yield=75%).

m.p.=109-111° C.

Example 1655-Chloro-1-[(3,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 164, the expected compound isobtained in the form of a white solid (yield=27%).

m.p.=136-138° C.

Example 1665-Chloro-1-[4-(1-methylethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(1-methylethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of a colorless oil (yield=88%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.41 (d, 1H); 7.77 (d, 2H); 7.38 (d, 1H);7.05 (d, 2H); 6.73 (s, 1H); 4.70 (sept., 1H); 3.59 (s, 3H); 3.04 (t,2H); 2.43 (t, 2H); 1.95 (quint., 2H); 1.24 (d, 6H).

Example 1675-Chloro-1-[4-(1-methylethoxy)phenylsulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 166, the expected compound isobtained in the form of a white solid (yield=97%).

m.p.=171° C.

Example 1685-Chloro-1-[(2-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and 2-methoxybenzenesulfonylchloride, the expected compound is obtained in the form of abeige-colored solid (yield=41%).

m.p.=115° C.

Example 1695-Chloro-1-[(2-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 168, the expected compound isobtained in the form of a white solid (yield=89%).

m.p.=197° C.

Example 1705-Chloro-1-[(2-chloro-3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-chloro-3-methylbenzenesulfonyl chloride, the expected compound isobtained in the form of a green oil (yield=57%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.18 (d, 1H); 7.87 (d, 1H); 7.79 (d, 1H);7.55 (t, 1H); 7.34 (d, 1H); 6.81 (s, 1H); 3.55 (s, 3H); 2.86 (t, 2H);2.35 (m, 5H); 1.85 (quint., 2H).

Example 1715-Chloro-1-[(2-chloro-3-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 170, the expected compound isobtained in the form of a white solid (yield=16%).

m.p.=171-174° C.

Example 1725-Chloro-1-[(2,4-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,4-difluorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a yellow oil (yield=82%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.26 (d, 1H); 8.17 (m, 1H); 7.59 (m, 1H);7.40 (m, 2H); 6.81 (s, 1H); 3.57 (s, 3H); 2.94 (t, 2H); 2.40 (t, 2H);1.89 (quint., 2H).

Example 1735-Chloro-1-[(2,4-difluorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 172, the expected compound isobtained in the form of a white solid (yield=8%).

m.p.=172-177° C.

Example 1745-Chloro-1-[(2-chloro-4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-chloro-4-methoxybenzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=75%).

m.p.=116-118° C.

Example 1755-Chloro-1-[(2-chloro-4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 174, the expected compound isobtained in the form of a white solid (yield=78%).

m.p.=154-156° C.

Example 1765-Chloro-1-[[4-(4-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(4-thiazolyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a white paste (yield=78%).

¹H NMR (300 MHz, DMSO-d₆) δ: 9.23 (d, 1H); 8.43 (m, 2H); 8.18 (d, 2H);7.95 (d, 2H); 7.40 (d, 1H); 6.77 (s, 1H); 3.58 (s, 3H); 3.09 (t, 2H);2.45 (t, 2H); 1.98 (quint., 2H).

Example 1775-Chloro-1-[[4-(4-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 176, the expected compound isobtained in the form of a white solid (yield=62%).

m.p.=211-217° C.

Example 1785-Chloro-1-[[4-(1,1-dimethylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-(1,1-dimethylethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=98%).

m.p.=107° C.

Example 1795-Chloro-1-[[4-(1,1-dimethylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 178, the expected compound isobtained in the form of a white solid (yield=89%).

m.p.=168° C.

Example 1805-Chloro-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation V and2,3-dihydro-1,4-benzodioxine-6-sulfonyl chloride, the expected compoundis obtained in the form of a brown oil (yield=23%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.41 (d, 1H); 7.35 (m, 3H); 7.03 (d, 1H);6.74 (s, 1H); 4.28 (m, 4H); 3.59 (s, 3H); 3.05 (t, 2H); 2.44 (t, 2H);1.94 (quint., 2H).

Example 1815-Chloro-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 180, the expected compound isobtained in the form of a white solid (yield=95%).

m.p.=166° C.

Example 1825-Chloro-1-[(2-pyridyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2-pyridinesulfonyl chloride, the expected compound is obtained in theform of a colorless oil (yield=50%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.61 (d, 1H); 8.24 (m, 3H); 7.74 (m, 1H);7.34 (d, 1H); 6.77 (s, 1H); 3.58 (s, 3H); 3.08 (t, 2H); 2.41 (t, 2H);1.94 (quint., 2H).

Example 1835-Chloro-1-[(2-pyridyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 182, the expected compound isobtained in the form of a white solid (yield=30%).

m.p.=187° C.

Example 1845-Chloro-1-[[3-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-(1-methylethyl)benzenesulfonyl chloride, the expected compound isobtained in the form of a brown solid (yield=73%).

m.p.=92° C.

Example 1855-Chloro-1-[[3-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 184, the expected compound isobtained in the form of a white solid (yield=37%).

m.p.=119° C.

Example 1865-Chloro-1-[(4-methyl-1-naphthalenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-methyl-1-naphthalenesulfonyl chloride, the expected compound isobtained in the form of a white solid (yield=85%).

m.p.=118-120° C.

Example 1875-chloro-1-[(4-methyl-1-naphthalenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 186, the expected compound isobtained in the form of a beige-colored solid (yield=13%).

m.p.=199-204° C.

Example 1881-[(3,5-Dimethylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with thecompound according to Preparation XXII and 3,5-dimethylbenzenesulfonylchloride, the expected compound is obtained in the form of a white solid(yield=51%).

m.p.=156-160° C.

Example 1891-[(3,5-Dimethylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 188, the expected compound isobtained in the form of a white solid (yield=33%).

m.p.=227-231° C.

Example 1905-Chloro-1-[(2,4-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,4-dichlorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a white solid (yield=22%).

m.p.=100-101° C.

Example 1915-Chloro-1-[(2,4-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 190, the expected compound isobtained in the form of a white solid (yield=96%).

m.p.=154-155° C.

Example 1925-Chloro-1-[(2,3-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with2,3-dichlorobenzenesulfonyl chloride, the expected compound is obtainedin the form of a pink oil (yield=40%).

¹H NMR (250 MHz, CDCl₃) δ: 8.18 (d, 1H); 7.83 (d, 1H); 7.74 (d, 1H);7.41 (t, 1H); 7.18 (d, 1H); 6.61 (s, 1H); 3.66 (s, 3H); 2.90 (t, 2H);2.39 (t, 2H); 2.03 (quint., 2H).

Example 1935-Chloro-1-[(2,3-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 192, the expected compound isobtained in the form of a white solid (yield=79%).

m.p.=173-174° C.

Example 1945-Chloro-1-[(3-chloro-2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with3-chloro-2-methylbenzenesulfonyl chloride, the expected compound isobtained in the form of a colorless paste (yield=84%).

¹H NMR (250 MHz, CDCl3) δ: 8.21 (d, 1H); 7.61 (d, 1H); 6.98 (m, 2H);6.95 (d, 1H); 6.65 (s, 1H); 3.66 (s, 3H); 2.87 (t, 2H); 2.55 (s, 3H);2.38 (t, 2H); 2.02 (quint., 2H).

Example 1955-Chloro-1-[(3-chloro-2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 194, the expected compound isobtained in the form of a white solid (yield=93%).

m.p.=127-128° C.

Example 1965-Chloro-1-[(4-methoxy-2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 76, starting with4-methoxy-2-methylbenzenesulfonyl chloride, the expected compound isobtained in the form of a white paste (yield=38%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.23 (d, 1H); 7.71 (d, 1H); 7.35 (d, 1H);6.98 (m, 2H); 6.78 (s, 1H); 3.82 (s, 3H); 3.55 (s, 3H); 2.81 (t, 2H);2.33 (t, 2H); 2.22 (s, 3H); 1.83 (quint., 2H)).

Example 1975-Chloro-1-[(4-methoxy-2-methylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 196, the expected compound isobtained in the form of a beige-colored solid (yield=40%).

m.p.=134-140° C.

Example 1981-[(1-Naphthalenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 188, starting with1-naphthalenesulfonyl chloride, the expected compound is obtained in theform of a colorless oil (yield=49%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.57 (d, 1H); 8.36 (m, 2H); 8.15 (m, 1H);7.82 (m, 2H); 7.69 (m, 3H); 7.00 (s, 1H); 3.52 (s, 3H); 2.92 (t, 2H);2.35 (t, 2H); 1.88 (quint., 2H).

Example 1991-[(1-Naphthalenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 198, the expected compound isobtained in the form of a beige-colored solid (yield=97%).

m.p.=195° C.

Example 2001-(1,3-Benzodioxol-5-ylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 188, starting with1,3-benzodioxole-5-sulfonyl chloride, the expected compound is obtainedin the form of a colorless oil (yield=45%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.82 (d, 1H); 7.78 (d, 1H); 7.54 (dd, 1H);7.42 (d, 1H); 7.08 (d, 1H); 6.91 (s, 1H); 6.15 (s, 2H); 3.59 (s, 3H);3.11 (t, 2H); 2.47 (t, 2H); 1.96 (quint., 2H).

Example 2011-(1,3-Benzodioxol-5-ylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 200, the expected compound isobtained in the form of a white solid (yield=44%).

m.p.=161° C.

Example 2021-[(3,4-Dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 188, starting with3,4-dihydro-4-methyl-2H-1,4-benzoxazine-7-sulfonyl chloride, theexpected compound is obtained in the form of a beige-colored solid(yield=27%).

m.p.=118° C.

Example 2031-[(3,4-Dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 202, the expected compound isobtained in the form of a pink solid (yield=39%).

m.p.=134° C.

Example 2041-[(2-Methyl-7-benzothiazolyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 188, starting with2-methyl-7-benzothiazolesulfonyl chloride, the expected compound isobtained in the form of a yellow oil (yield=9%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.60 (d, 1H); 8.30 (d, 1H); 7.91 (d, 1H);7.83 (d, 1H); 7.70 (t, 1H); 6.98 (s, 1H); 3.54 (s, 3H); 2.99 (t, 2H);2.83 (s, 3H); 2.38 (t, 2H); 1.90 (quint., 2H).

Example 2051-[(2-Methyl-7-benzothiazolyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 204, the expected compound isobtained in the form of a beige-colored solid (yield=48%).

m.p.=187° C.

Example 2065-(Trifluoromethyl)-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation XXII and2,3-dihydro-1,4-benzodioxine-6-sulfonyl chloride, the expected compoundis obtained in the form of a colorless oil (yield=13%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.63 (d, 1H); 7.79 (d, 1H); 7.39 (m, 2H);7.04 (d, 1H); 6.92 (s, 1H); 4.28 (m, 4H); 3.60 (s, 3H); 3.10 (t, 2H);2.47 (t, 2H); 1.99 (quint., 2H).

Example 2075-(Trifluoromethyl)-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 206, the expected compound isobtained in the form of a white solid (yield=88%).

m.p.=158° C.

Example 2081-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-pentanoicacid, methyl ester

By working in a manner similar to that of Preparation VI, starting withthe compound according to Preparation XXIII and benzothiazole-6-sulfonylchloride, the expected compound is obtained in the form of a colorlesspaste (yield=36%).

¹H NMR (250 MHz, DMSO-d₆) δ: 9.68 (s, 1H); 9.02 (d, 1H); 8.46 (d, 1H);8.23 (d, 1H); 7.92 (dd, 1H); 7.39 (d, 1H); 6.75 (s, 1H); 3.58 (s, 3H);3.06 (t, 2H); 2.34 (t, 2H); 1.66 (m, 4H).

Example 2091-(6-Benzothiazolylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-pentanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 208, the expected compound isobtained in the form of a gray solid (yield=43%).

m.p.=169° C.

Example 2102-[[5-Chloro-1-[(4-ethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXIV, the expected compound isobtained in the form of a yellow oil (yield=74%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.42 (d, 1H); 7.92 (d, 2H); 7.45 (d, 1H);7.42 (d, 2H); 6.90 (s, 1H); 4.87 (s, 2H); 3.66 (s, 3H): 2.65 (q, 2H);1.45 (s, 6H); 1.13 (t, 3H).

Example 2112-[[5-Chloro-1-[(4-ethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 210, the expected compound isobtained in the form of a white solid (yield=14%).

m.p.=172° C.

Example 2122-[[5-Chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXV, the expected compound is obtainedin the form of a yellow paste (yield=27%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.41 (d, 1H); 7.96 (d, 2H); 7.40 (d, 1H);7.10 (d, 2H); 6.88 (s, 1H); 4.87 (s, 2H); 3.81 (s, 3H); 3.67 (s, 3H);1.47 (s, 6H).

Example 2132-[[5-Chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 212, the expected compound isobtained in the form of a white solid (yield=57%).

m.p.=199° C.

Example 2142-[[5-Chloro-1-[(2,3-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXVI, the expected compound isobtained in the form of a colorless paste (yield=41%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.20 (d, 1H); 8.06 (dd, 1H); 7.72 (dd, 1H);7.62 (t, 1H); 7.41 (d, 1H); 7.01 (s, 1H); 4.75 (s, 2H); 3.61 (s, 3H);1.24 (s, 6H).

Example 2152-[[5-Chloro-1-[(2,3-dichlorophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 214, the expected compound isobtained in the form of a yellow solid (yield=16%).

m.p.=174° C.

Example 2162-[[5-Chloro-1-[[4-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXVII, the expected compound isobtained in the form of a white solid (yield=87%).

m.p.=120° C.

Example 2172-[[5-Chloro-1-[[4-(1-methylethyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 216, the expected compound isobtained in the form of a yellow solid (yield=39%).

m.p.=190° C.

Example 2182-[[5-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXVIII, the expected compound isobtained in the form of a white solid (yield=54%).

m.p.=108° C.

Example 2192-[[5-Chloro-1-(1-naphthalenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 218, the expected compound isobtained in the form of a bluish solid (yield=36%).

m.p.=209° C.

Example 2202-[[5-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXIX, the expected compound isobtained in the form of a brown foam (yield=66%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.77 (dd, 1H); 8.67 (dd, 1H); 8.51 (dd,1H); 8.42 (dd, 1H); 8.24 (d, 1H); 7.65 (t, 1H); 7.28 (m, 1H); 7.20 (d,1H); 6.76 (s, 1H); 5.11 (s, 2H); 3.63 (s, 3H); 1.39 (s, 6H).

Example 2212-[[5-Chloro-1-(8-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 220, the expected compound isobtained in the form of a beige-colored solid (yield=14%).

m.p.=223° C.

Example 2222-[[5-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXX, the expected compound is obtainedin the form of a brown oil (yield=37%).

¹H NMR (250 MHz, DMSO-d₆) δ: 8.20 (d, 1H); 7.52 (d, 1H); 7.36 (d, 1H);7.32 (dd, 1H); 7.14 (d, 1H); 6.81 (s, 1H); 4.77 (s, 2H); 3.82 (s, 3H);3.64 (s, 3H); 3.48 (s, 3H); 1.37 (s, 6H).

Example 2232-[[5-Chloro-1-[(2,5-dimethoxyphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 222, the expected compound isobtained in the form of a beige-colored solid (yield=23%).

m.p.=200° C.

Example 2242-[[1-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXXI, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=131° C.

Example 2252-[[1-(1,3-Benzodioxol-5-ylsulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 224, the expected compound isobtained in the form of a white solid (yield=39%).

m.p.=172° C.

Example 2262-[[5-Chloro-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXXII, the expected compound isobtained in the form of a brown oil (yield=91%).

¹H NMR (500 MHz, DMSO-d₆) δ: 8.41 (d, 1H); 7.58 (m, 2H); 7.41 (d, 1H);7.13 (d, 1H); 6.87 (s, 1H); 4.87 (s, 2H); 4.30 (m, 4H); 3.67 (s, 3H);1.47 (s, 6H).

Example 2272-[[5-Chloro-1-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 226, the expected compound isobtained in the form of a beige-colored solid (yield=59%).

m.p.=213° C.

Example 2282-[[5-Chloro-1-(2,3-dihydro-5-benzofuransulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXXIII, the expected compound isobtained in the form of a yellow oil (yield=99%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.40 (d, 1H); 7.91 (d, 1H); 7.83 (dd, 1H);7.40 (d, 1H); 6.93 (d, 1H); 6.87 (s, 1H); 4.89 (s, 2H); 4.62 (t, 2H);3.67 (s, 3H); 3.20 (t, 2H); 1.47 (s, 6H).

Example 2292-[[5-Chloro-1-(2,3-dihydro-5-benzofuransulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 228, the expected compound isobtained in the form of a beige-colored solid (yield=26%).

m.p.=169° C.

Example 2302-[[5-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXXIV, the expected compound isobtained in the form of a brown oil (yield=99%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.40 (d, 1H); 7.64 (s, 2H); 7.40 (d, 1H);7.38 (s, 1H); 6.89 (s, 1H); 4.90 (s, 2H); 3.66 (s, 3H); 2.31 (s, 6H);1.45 (s, 6H).

Example 2312-[[5-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 230, the expected compound isobtained in the form of a beige-colored solid (yield=40%).

m.p.=154° C.

Example 2322-[[5-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)-sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid, methyl ester

By working in a manner similar to that of Example 42, starting with thecompound according to Preparation XXXV, the expected compound isobtained in the form of a brown oil (yield=99%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.44 (d, 1H); 7.39 (d, 1H); 7.15 (dd, 1H);6.98 (d, 1H); 6.82 (m, 2H); 4.87 (s, 2H); 4.25 (t, 2H); 3.66 (s, 3H);3.26 (t, 2H); 2.83 (s, 3H); 1.45 (s 6H).

Example 2332-[[5-Chloro-1-[(3,4-dihydro-4-methyl-2H-1,4-benzoxazin-7-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]-2-methylpropanoicacid

By working in a manner similar to that of Example 43, starting with theester obtained according to Example 232, the expected compound isobtained in the form of a pink solid (yield=37%).

m.p.=229° C.

Example 234(2S)-2-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, ethyl ester

a)—Ethyl ester of (2S)-2-(2-propynyloxy)propanoic acid: this compound isobtained, in a yield of 24%, by reacting propargyl bromide with theethyl ester of (S)-(−)-lactic acid sodium-treated beforehand with sodiumhydride in THF (colorless liquid; b.p.=70-73° C. at 13 hPa).

b)—By working in a manner similar to that of Example 1, starting withthe ester obtained in a) above, the expected compound is obtained in theform of a yellow oil (yield=19%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.42 (d, 1H); 8.02 (d, 2H); 7.74 (m, 1H);7.60 (m, 2H); 7.43 (d, 1H); 6.95 (s, 1H); 5.04 (d, 1H); 4.92 (d, 1H);4.23 (q, 1H); 4.12 (q, 2H); 1.31 (d, 3H); 1.16 (t, 3H)

Example 235(2S)-2-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 234, the expected compound isobtained in the form of a pink solid (yield=33%).

m.p.=154° C.

[α]_(D)=−50° (c=0.39; MeOH).

Example 236(2R)-2-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]methoxy]propanoicacid, methyl ester

By working in a manner similar to that of Example 234, starting with themethyl ester of (R)-(+)-lactic acid, the following are obtained:

a)—Methyl ester of (2R)-2-(2-propynyloxy)propanoic acid: (colorlessliquid; b.p.=81-88° C. at atmospheric pressure).b)—The expected compound in the form of a yellow oil (yield=73%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.42 (d, 1H); 8.01 (dd, 2H); 7.73 (m, 1H);7.63 (m, 2H); 7.43 (d, 1H); 6.96 (s, 1H); 5.05 (d, 1H); 4.92 (d, 1H);4.26 (q, 1H); 3.66 (s, 3H); 1.31 (d, 3H).

Example 237(2R)-2-[[5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 236, the expected compound isobtained in the form of a white solid (yield=58%).

m.p.=150° C.

[α]_(D)=+50° (c=0.375; MeOH).

Example 238(2S)-2-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid, ethyl ester

By working in a manner similar to that of Example 234, starting with thecompound according to Preparation VII, the expected compound is obtainedin the form of a yellow oil (yield=91%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.63 (d, 1H); 8.06 (dd, 2H); 7.84 (d, 1H);7.74 (m, 1H); 7.62 (m, 2H); 7.12 (s, 1H); 5.10 (d, 1H); 4.97 (d, 1H);4.26 (q, 1H); 4.15 (q, 2H); 1.31 (d, 3H); 1.18 (t, 3H).

Example 239(2S)-2-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 238, the expected compound isobtained in the form of a beige-colored solid (yield=60%).

m.p.=142° C.

[α]_(D)=−46° (c=0.52; MeOH).

Example 240(2R)-2-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid, methyl ester

By working in a manner similar to that of Example 236, starting with thecompound according to Preparation VII, the expected compound is obtainedin the form of a yellow oil (yield=88%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.63 (d, 1H); 8.06 (d, 2H); 7.83 (d, 1H);7.75 (m, 1H); 7.62 (t, 2H); 7.13 (s, 1H); 5.10 (d, 1H); 4.96 (d, 1H);4.28 (q, 1H); 3.66 (s, 3H); 1.31 (d, 3H).

Example 241(2R)-2-[[1-(Phenylsulfonyl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyrid-2-yl]-methoxy]propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 240, the expected compound isobtained in the form of a beige-colored solid (yield=78%).

m.p.=140° C.

[α]_(D)=+39° (c=0.39; MeOH).

Example 2425-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid,methyl ester

By working in a manner similar to that of Example 1, starting with thecompound according to Preparation XXXVI, the expected compound isobtained in the form of a brown solid (yield=56%).

m.p.=98-115° C.

Example 2435-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 242, the expected compound isobtained in the form of a yellow solid (yield=21%).

m.p.=88-92° C.

Example 2445-Methoxy-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propanoic acid,methyl ester

By working in a manner similar to that of Example 1, starting with thecompound according to Preparation XXXVIII, the expected compound isobtained in the form of a white solid (yield=63%).

m.p.=145-150° C.

Example 2455-Methoxy-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-propa-noic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 244, the expected compound isobtained in the form of a beige-colored solid (yield=75%).

m.p.=136-139° C.

Example 2465-Methoxy-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid,methyl ester

By working in a manner similar to that of Example 1, starting with thecompound according to Preparation XL, the expected compound is obtainedin the form of a yellow solid (yield=86%).

m.p.=113-114° C.

Example 2475-Methoxy-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 246, the expected compound isobtained in the form of a beige-colored solid (yield=34%).

m.p.=190-198° C.

Example 2485-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid,methyl ester

By working in a manner similar to that of Example 242, starting with themethyl ester of 5-hexynoic acid, the expected compound is obtained inthe form of a yellow solid (yield=92%).

m.p.=91-94° C.

Example 2495-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 248, the expected compound isobtained in the form of a yellow solid (yield=38%).

m.p.=172-180° C.

Example 2501-(6-Benzothiazolylsulfonyl)-5-methyl-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 248, starting with thecompound according to Preparation XLI, the expected compound is obtainedin the form of a yellow solid (yield=76%).

¹H NMR (300 MHz, DMSO-d₆) δ: 9.65 (s, 1H); 8.97 (d, 1H); 8.29 (d, 1H);8.20 (d, 1H); 7.85 (dd, 1H); 7.17 (d, 1H); 6.66 (s, 1H); 3.58 (s, 3H);3.10 (t, 2H); 2.49 (s, 3H); 2.41 (t, 2H); 1.99 (quint., 2H).

Example 2511-(6-Benzothiazolylsulfonyl)-5-methyl-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 250, the expected compound isobtained in the form of a violet-colored solid (yield=14%).

m.p.=67-70° C.

Example 2525-Chloro-1-(3-pyridylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 248, starting with thecompound according to Preparation XLII, the expected compound isobtained in the form of a white solid (yield=57%).

m.p.=119° C.

Example 2535-Chloro-1-(3-pyridylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 252, the expected compound isobtained in the form of a white solid (yield=73%).

m.p.=181° C.

Example 2545-Chloro-1-(6-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 248, starting with thecompound according to Preparation XLIII, the expected compound isobtained in the form of a brown solid (yield=72%).

m.p.=133-141° C.

Example 2555-Chloro-1-(6-quinolylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 254, the expected compound isobtained in the form of a beige-colored solid (yield=40%).

m.p.=153-162° C.

Example 2565-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-pentanoic acid,methyl ester

By working in a manner similar to that of Example 1, starting with themethyl ester of heptynoic acid, the expected compound is obtained in theform of a white solid (yield=37%).

m.p.=73° C.

Example 2575-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-pentanoic acid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 256, the expected compound isobtained in the form of a beige-colored solid (yield=69%).

m.p.=113° C.

Example 2585-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-pentanoicacid, methyl ester

By working in a manner similar to that of Example 256, starting with thecompound according to Preparation XXXIV, the expected compound isobtained in the form of a beige-colored solid (yield=84%).

m.p.=126° C.

Example 2595-Chloro-1-[(3,5-dimethylphenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-pentanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 258, the expected compound isobtained in the form of a white solid (yield=84%).

m.p.=160° C.

Example 2605-Chloro-α,α-dimethyl-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid,

By working in a manner similar to that of Example 1, starting with2,2-dimethylhexynoic acid, the expected compound is obtained in the formof a beige-colored solid (yield=14%).

m.p.=197° C.

Example 2611-(6-Benzothiazolylsulfonyl)-5-chloro-α,α-dimethyl-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 1, starting with2,2-dimethylhexynoic acid and the compound according to PreparationXLIV, the expected compound is obtained in the form of a beige-coloredsolid (yield=8%).

m.p.=21° C.

Example 2621-[[4-(1-Methylethyl)phenyl]sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

A solution of 0.263 g (0.92 mM) of the compound according to PreparationXLV in 10 ml of DMF is prepared and 73 mg (1.8 mM) of sodium hydride asa 60% suspension in oil are added at 0° C. The mixture is stirred for 15minutes at 0° C., and 0.302 g (1.4 mM) of4-(1-methylethyl)benzenesulfonamide chloride is then added. The reactionmedium is stirred for 60 hours at room temperature and then poured intoa mixture of crushed ice and ammonium chloride, and extracted with ethylacetate. The organic phase obtained is dried over magnesium sulfate andconcentrated under reduced pressure.

The expected compound is thus obtained in the form of a brown solid(yield=93%).

m.p.=78° C.

Example 2631-[[4-(1-Methylethyl)phenyl]sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 262, the expected compound isobtained in the form of a pale green solid (yield=50%).

m.p.=144° C.

Example 2641-[(4-Chlorophenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 262, starting with4-chlorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a white solid (yield=47%).

m.p.=97° C.

Example 2651-[(4-Chlorophenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 264, the expected compound isobtained in the form of a pale green solid (yield=37%).

m.p.=176° C.

Example 2661-[(2-Chlorophenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 262, starting with2-chlorobenzenesulfonyl chloride, the expected compound is obtained inthe form of a beige-colored solid (yield=71%).

m.p.=88° C.

Example 2671-[(2-Chlorophenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 266, the expected compound isobtained in the form of a pale green solid (yield=50%).

m.p.=171° C.

Example 2681-[[(3-(Trifluoromethoxy)phenyl]sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 262, starting with3-(trifluoromethoxy)benzenesulfonyl chloride, the expected compound isobtained in the form of an ochre-colored solid (yield=88%).

m.p.=72° C.

Example 2691-[[(3-(Trifluoromethoxy)phenyl]sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 268, the expected compound isobtained in the form of a beige-colored solid (yield=27%).

m.p.=164° C.

Example 2701-[(4-Bromophenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with theester according to Preparation V and 4-bromobenzenesulfonamide chloride,the expected compound is obtained in the form of a white solid(yield=97%).

m.p.=102° C.

Example 2715-Chloro-1-[[4-(4-morpholinyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

1.5 mg of tris(benzylideneacetone)dipalladium, 2 mg ofdi(t-butyl)([1,1′-biphenyl]2-yl)phosphine, 48 mg (0.22 mM) of potassiumphosphate, 75 mg (0.159 mM) of the compound obtained according toExample 270 and 0.16 ml of DME are placed in a reactor tube adapted forheating by microwave, while maintaining under an argon atmosphere. Thesecompounds are mixed together and 17 mg (0.19 mM) of morpholine and 0.32ml of DME are added. This reaction mixture is heated by microwave at110° C. for 2 hours and then concentrated under reduced pressure. Theresidue is purified by chromatography on silica gel, eluting with atoluene/ethyl acetate mixture (as a gradient from 9/1 to 8/2; v/v). Theexpected compound is thus obtained in the form of a white solid(yield=80%).

m.p.=110° C.

Example 2725-Chloro-1-[[4-(4-morpholinyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 271, the expected compound isobtained in the form of a white solid (yield=55%).

m.p.=176° C.

Example 2735-Chloro-1-[[4-(1-pyrrolidinyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 271, starting withpyrrolidine, the expected compound is obtained in the form of a whitesolid (yield=63%).

m.p.=121° C.

Example 2745-Chloro-1-[[4-(1-pyrrolidinyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 273, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=88° C.

Example 2755-Chloro-1-[[4-(dimethylamino)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 271, starting withdimethylamine as a 2 N solution in THF, the expected compound isobtained in the form of a white solid (yield=35%).

m.p.=188° C.

Example 2765-Chloro-1-[[4-(dimethylamino)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 275, the expected compound isobtained in the form of a white solid (yield=99%).

m.p.=76° C.

Example 2775-Chloro-1-[(3-bromophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with theester according to Preparation V and 3-bromobenzenesulfonamide chloride,the expected compound is obtained in the form of a white solid(yield=97%).

m.p.=109° C.

Example 2785-Chloro-1-[[3-(dimethylamino)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 275, starting withdimethylamine as a 2 N solution in THF and the bromo derivative obtainedaccording to Example 277, the expected compound is obtained in the formof a beige-colored solid (yield=6%).

m.p.=96-97° C.

Example 2795-Chloro-1-[(4-iodophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 52, starting with theester according to Preparation V and 4-iodobenzenesulfonamide chloride,the expected compound is obtained in the form of a beige-colored solid(yield=70%).

m.p.=117-118° C.

Example 2805-Chloro-1-[[4-(2-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A solution of 249 mg (0.48 mM) of the compound obtained according toExample 279 in 2.5 ml of toluene is prepared in a reactor tube adaptedfor heating by microwave, and 110 mg (0.096 mM) oftetrakis(triphenyl)phosphine and then 0.15 ml of2-(tributylstannyl)thiazole and 0.4 ml of N-methylpyrrolidinone areadded. The mixture is then heated at 100° C. by microwave for 1 hour 30minutes. After cooling, water is added and the resulting mixture isextracted with diethyl ether. The organic phase obtained is washed withwater and then dried over magnesium sulfate and concentrated underreduced pressure. The crude product obtained is purified bychromatography on silica gel, eluting with a petroleum ether/diethylether mixture (6/4; v/v). The purified compound is recrystallized from amixture of diethyl ether and petroleum ether. The expected compound isobtained in the form of a yellow solid (yield=57%).

m.p.=101° C.

Example 2815-Chloro-1-[[4-(2-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 280, the expected compound isobtained in the form of a white solid (yield=44%).

m.p.=214-215° C.

Example 2825-Chloro-1-[[3-(2-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 280, starting with thebromo derivative obtained according to Example 277, the expectedcompound is obtained in the form of a white solid (yield=32%).

m.p.=82-86° C.

Example 2835-Chloro-1-[[3-(2-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 282, the expected compound isobtained in the form of a white solid (yield=68%).

m.p.=187-188° C.

Example 2845-Chloro-1-[[3-(5-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 282, starting with thebromo derivative obtained according to Example 277 and5-(tributylstannyl)thiazole, the expected compound is obtained in theform of a white solid (yield=71%).

m.p.=147-148° C.

Example 2855-Chloro-1-[[3-(5-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 284, the expected compound isobtained in the form of a white solid (yield=45%).

m.p.=157-160° C.

Example 2865-Chloro-1-[[3-(4-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 282, starting with thebromo derivative obtained according to Example 277 and4-(tributylstannyl)thiazole, the expected compound is obtained in theform of a white solid (yield=38%).

m.p.=147-148° C.

Example 2875-Chloro-1-[[3-(4-thiazolyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 286, the expected compound isobtained in the form of a white solid (yield=4%).

m.p.=185-186° C.

Example 2885-Chloro-1-[[4-(2-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 280, starting with thebromo derivative obtained according to Example 270 and2-(tributylstannyl)pyridine, the expected compound is obtained in theform of an orange-colored solid (yield=61%).

m.p.=123-124° C.

Example 2895-Chloro-1-[[4-(2-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 288, the expected compound isobtained in the form of a beige-colored solid (yield=40%).

m.p.=214-215° C.

Example 2905-Chloro-1-[[4-(3-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A mixture of 300 mg (0.63 mM) of the compound obtained according toExample 270, 98 mg (0.80 mM) of 3-pyridineboronic acid and 0.9 ml of a 2M solution of potassium carbonate in 5 ml of DME is prepared in areactor tube adapted for heating by microwave, and 6 mg of PdCl₂dppf areadded. The mixture is then heated at 120° C. by microwave for 1 hour.After cooling, water is added and the resulting mixture is extractedwith ethyl acetate. The organic phase obtained is washed with water andthen dried over magnesium sulfate and concentrated under reducedpressure. The crude product obtained is purified by chromatography onsilica gel, eluting with a cyclohexane/ethyl acetate mixture (80/20 andthen 70/30; v/v). The expected compound is thus obtained in the form ofa colorless oil (yield=37%).

¹H NMR (300 MHz, DMSO-d₆) δ: 8.90 (d, 1H); 8.63 (dd, 1H); 8.47 (d, 1H);8.11 (m, 1H); 7.97 (m, 4H); 7.51 (m, 1H); 7.41 (d, 1H); 6.79 (s, 1H);3.58 (s, 3H); 3.10 (t, 2H); 2.49 (s, 3H); 2.46 (t, 2H); 1.99 (quint.,2H).

Example 2915-Chloro-1-[[4-(3-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 290, the expected compound isobtained in the form of a white solid (yield=92%).

m.p.=141° C.

Example 2925-Chloro-1-[[4-(4-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 290, starting with4-pyridineboronic acid, the expected compound is obtained in the form ofa white solid (yield=70%).

m.p.=215° C.

Example 2935-Chloro-1-[[4-(4-pyridyl)phenyl]sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 292, the expected compound isobtained in the form of a white solid (yield=77%).

m.p.=174° C.

Example 2945-Chloro-1-[(4-fluoro-3-nitrophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with theester according to Preparation XLVI, the expected product is obtained inthe form of a yellow solid (yield=88%).

m.p.=129-131° C.

Example 2951-[(5-Benzothiazolyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A solution of 0.21 g (0.46 mM) of the compound obtained according toExample 294 in 2 ml of pyridine is prepared and 0.323 g (4.37 mM) ofsodium hydrogen sulfide monohydrate suspended in 2 ml of ethylene glycolis added, at room temperature, followed by addition of 1 ml of pyridine.The mixture is stirred for 30 minutes at room temperature, and thenpoured into a mixture of water and ice. The mixture is brought to pH 2by adding dilute hydrochloric acid, and is extracted with ethyl acetate.The organic phase obtained is washed with N hydrochloric acid solution,and then with water, dried over magnesium sulfate and concentrated underreduced pressure. The crude product obtained is purified bychromatography on silica gel, eluting with a toluene/ethyl acetatemixture (90/10 and then 75/25; v/v). 160 mg of the methyl ester of5-chloro-1-[(4-mercapto-3-nitrophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid (yellow oil) are thus obtained. This compound is redissolved in 4ml of acetic acid and 99 mg (1.7 mM) of iron powder are added, withstirring and at room temperature. The reaction mixture is stirred at 70°C. for 2 hours and then concentrated under reduced pressure. Theevaporation residue is taken up in water and ethyl acetate. The aqueousphase is separated out and re-extracted with ethyl acetate. The combinedorganic phases are washed with water, with sodium carbonate solution andthen with brine, dried over magnesium sulfate and concentrated underreduced pressure. 150 mg of the methyl ester of1-[(3-amino-4-mercaptophenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid (orange foam, not purified) are thus obtained. This product istaken up in 3 ml of formic acid and 80 mg of zinc powder are added withstirring. The reaction mixture is stirred for 3 hours at 100° C., andthen cooled and poured into water. This aqueous phase is brought to pH 4by adding N sodium hydroxide solution and is extracted with ethylacetate. The organic phase obtained is washed with sodium bicarbonatesolution, with N sodium hydroxide solution and then with water, driedover magnesium sulfate and concentrated under reduced pressure. Thecrude product obtained is purified by chromatography on silica gel,eluting with a toluene/ethyl acetate mixture (95/5 and then 80/20; v/v).The expected compound is thus obtained in the form of a colorless oil(yield=47%).

¹H NMR (500 MHz, DMSO-d₆) δ: 9.62 (s, 1H); 8.61 (s, 1H); 8.53 (d, 1H);8.44 (d, 1H); 7.90 (dd, 1H); 7.40 (d, 1H); 6.78 (s, 1H); 3.59 (s, 3H);3.13 (t, 2H); 2.46 (t, 2H); 1.99 (quint., 2H).

Example 2965-Chloro-1-[(5-benzothiazolyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 295, the expected compound isobtained in the form of a white solid (yield=24%).

m.p.=202-206° C.

Example 2971-[(4-Amino-3-nitrophenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A mixture of 400 mg (0.874 mM) of the compound obtained according toExample 294 in 4 ml of dioxane is prepared and 0.31 ml 32% is addedcautiously, with stirring. The reaction mixture is kept stirring for onehour, at room temperature, and 20 ml of ethyl acetate are then added.This organic phase is washed with water and then with brine, dried overmagnesium sulfate and concentrated under reduced pressure. 375 mg of theexpected compound are thus obtained in the form of a yellow solid(yield=95%).

m.p.=154-156° C.

Example 2985-Chloro-1-[(3,4-diaminophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A solution of 365 mg (0.806 mM) of the compound obtained according toExample 297 in 5 ml of acetic acid is prepared and 225 mg (4.03 mM) ofiron powder are added, with stirring and at room temperature. Thereaction mixture is stirred at 70° C. for 3 hours and then concentratedunder reduced pressure. The evaporation residue is taken up in water andethyl acetate. The aqueous phase is separated out and re-extracted withethyl acetate. The combined organic phases are washed with water, withsodium carbonate solution and then with brine, dried over magnesiumsulfate and concentrated under reduced pressure. 313 mg of the expectedcompound are thus obtained in the form of a yellow solid (yield=92%).

m.p.=162-164° C.

Example 2991-[(6-Benzopyrazinyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A mixture of 150 mg (0.355 mM) of the compound obtained according toExample 298 in 1.25 ml of acetonitrile is prepared and 0.11 ml (0.95 mM)of glyoxal is added, with stirring. The reaction mixture is keptstirring for 14 hours, at 50° C., and then concentrated under reducedpressure and taken up in 10 ml of ethyl acetate. This organic phase iswashed with water and then with brine, dried over magnesium sulfate andconcentrated under reduced pressure. The crude product obtained ispurified by chromatography on silica gel, eluting with a toluene/ethylacetate mixture (95/5 and then 80/20; v/v). The expected compound isthus obtained in the form of a yellow solid (yield=58%).

¹H NMR (250 MHz, DMSO) δ: 9.12 (m, 2H); 8.65 (d, 1H); 8.53 (d, 1H); 8.28(d, 1H); 8.09 (dd, 1H); 7.41 (d, 1H); 6.81 (s, 1H); 3.56 (s, 3H); 3.12(t, 2H); 2.45 (t, 2H); 1.98 (quint., 2H).

Example 3001-[(6-Benzopyrazinyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 299, the expected compound isobtained in the form of a beige-colored solid (yield=31%).

m.p.=103-106° C.

Example 3015-Chloro-1-[(2,3-dihydro-1H-indol-5-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 104, the expected compound isobtained in the form of a beige-colored solid (yield=37%).

m.p.=190° C.

Example 3025-Chloro-1-[(2,3-dihydro-1H-indol-5-yl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-propanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 66, the expected compound isobtained in the form of a green solid (yield=19%).

m.p.=79° C.

Example 3031-[(2,1,3-Benzothiadiazol-4-yl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 3, starting with theester according to Preparation XLVII, the expected compound is obtainedin the form of a brown solid (yield=70%).

m.p.=112° C.

Example 3041-[(5-Benzopyrazinyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

A solution of 253 mg (0.56 mM) of the compound obtained according toExample 303 in 17 ml of acetic acid is prepared and 364 mg (5.6 mM) ofzinc powder are added, with stirring and at room temperature. Thereaction mixture is stirred under gentle reflux for 7 hours and thencooled and filtered through a Whatman filter. The filtrate isconcentrated under reduced pressure. The yellow solid obtained (methylester of5-chloro-1-[(2,3-diaminophenyl)sulfonyl]-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid) is taken up in 25 ml of methanol, and 242 mg (1.7 mM) of glyoxal,0.025 ml of acetic acid and 46 mg (0.56 mM) of sodium acetate are added.The reaction mixture is refluxed for 3 hours 30 minutes and then cooledand diluted with ethyl acetate. The organic phase is washed with waterand then with, dried over magnesium sulfate and concentrated underreduced pressure. The crude product obtained is purified bychromatography on silica gel, eluting with a cyclohexane/ethyl acetatemixture (50/50; v/v). The expected compound is thus obtained in the formof a yellow solid (yield=73%).

m.p.=71° C.

Example 3051-[(5-Benzopyrazinyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 304, the expected compound isobtained in the form of a yellow solid (yield=88%).

m.p.=74° C.

Example 3061-[(4-Bromo-2-chlorophenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 277, starting with4-bromo-2-chlorobenzenesulfonamide chloride, the expected compound isobtained in the form of a pale yellow solid (yield=87%).

¹H NMR (300 MHz, CDCl₃) δ: 8.17 (d, 1H); 7.85 (d, 1H); 7.66 (d, 1H);7.60 (dd, 1H); 7, 18 (d, 1H); 6.59 (s, 1H); 3.67 (s, 3H); 2.89 (t, 2H);2.39 (t, 2H); 2.02 (quint., 2H).

Example 3071-[[2-Chloro-4-(dimethylamino)phenyl]sulfonyl]-5-chloro-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 275, starting with thecompound obtained according to Example 306, the expected compound isobtained in the form of a white solid (yield=36%).

m.p.=123-124° C.

Example 3081-[[2-Chloro-4-(dimethylamino)phenyl]sulfonyl]-5-chloro-1H-pyrrolo-[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 307, the expected compound isobtained in the form of a white solid (yield=67%).

m.p.=208° C.

Example 3091-[(2-Chloro-4-methylphenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid, methyl ester

By working in a manner similar to that of Example 277, starting with2-chloro-4-methylbenzenesulfonamide chloride, the expected compound isobtained in the form of a white solid (yield=74%).

m.p.=88-89° C.

Example 3101-[(2-Chloro-4-methylphenyl)sulfonyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-butanoicacid

By working in a manner similar to that of Example 2, starting with theester obtained according to Example 309, the expected compound isobtained in the form of a white solid (yield=82%).

m.p.=168-169° C.

The compounds according to the invention described above are listed inthe following table:

TABLE I

Ex. R₁ X^((*)) R₃ R₄ n Ar R  1 5-Cl ls H H 1

CH₃  2 5-Cl ls H H 1

H  3 5-Cl ls H H 2

CH₃  4 5-Cl ls H H 2

H  5 5-Cl O CH₃ H 1

C₂H₅  6 5-Cl O CH₃ H 1

H  7 5-Cl O CH₃ CH₃ 1

CH₃  8 5-Cl O CH₃ CH₃ 1

H  9 5-Cl ls H H 2

CH₃ 10 5-Cl ls H H 2

H 11 5-Cl ls CH₃ CH₃ 1

CH₃ 12 5-Cl ls CH₃ CH₃ 1

H 13 5-CF₃ O CH₃ H 1

C₂H₅ 14 5-CF₃ O CH₃ H 1

H 15 5-CF₃ O CH₃ CH₃ 1

CH₃ 16 5-CF₃ O CH₃ CH₃ 1

H 17 5-CF₃ ls H H 1

CH₃ 18 5-CF₃ ls H H 1

H 19 5-CF₃ ls H H 2

CH₃ 20 5-CF₃ ls H H 2

H 21 5-Cl ls H H 2

CH₃ 22 5-Cl ls H H 2

H 23 5-Cl ls H H 2

CH₃ 24 5-Cl ls H H 2

H 25 5-Cl ls H H 2

CH₃ 26 5-Cl ls H H 2

H 27 5-Cl ls H H 2

CH₃ 28 5-Cl ls H H 2

H 29 5-Cl ls H H 2

CH₃ 30 5-Cl ls H H 2

H 31 5-Cl ls H H 2

CH₃ 32 5-Cl ls H H 2

H 33 5-Cl ls H H 1

CH₃ 34 5-Cl ls H H 1

H 35 5-Cl ls H H 1

CH₃ 36 5-Cl ls H H 1

H 37 5-Cl ls H H 1

Na Ex. R₁ X^((*)) R₃ R₄ N Ar R 38 5-Cl O CH₃ H 1

C₂H₅ 39 5-Cl O CH₃ H 1

H 40 5-Cl O CH₃ H 1

C₂H₅ 41 5-Cl O CH₃ H 1

H 42 5-Cl O CH₃ CH₃ 1

CH₃ 43 5-Cl O CH₃ CH₃ 1

H 44 5-Cl O CH₃ H 1

C₂H₅ 45 5-Cl O CH₃ H 1

H 46 5-Cl O CH₃ H 1

C₂H₅ 47 5-Cl O CH₃ H 1

H 48 5-CF₃ O CH₃ CH₃ 1

CH₃ 49 5-CF₃ O CH₃ CH₃ 1

H 50 5-Cl O CH₃ H 1

C₂H₅ 51 5-Cl O CH₃ H 1

H 52 5-CF₃ O CH₃ H 1

C₂H₅ 53 5-CF₃ O CH₃ H 1

H 54 5-Cl ls H H 1

CH₃ 55 5-Cl ls H H 1

H 56 5-Cl ls H H 1

CH₃ 57 5-Cl ls H H 1

H 58 5-Cl ls H H 1

CH₃ 59 5-Cl ls H H 1

H 60 5-Cl ls H H 1

CH₃ 61 5-Cl ls H H 1

H 62 5-Cl ls H H 1

CH₃ 63 5-Cl ls H H 1

H 64 5-Cl ls H H 1

CH₃ 65 5-Cl ls H H 1

H 66 5-Cl ls H H 1

CH₃ 67 5-Cl ls H H 1

H 68 5-Cl ls H H 1

CH₃ 69 5-Cl ls H H 1

H 70 5-CF₃ ls H H 1

CH₃ 71 5-CF₃ ls H H 1

H 72 5-CF₃ ls H H 1

CH₃ 73 5-CF₃ ls H H 1

H 74 5-CF₃ ls H H 1

CH₃ 75 5-CF₃ ls H H 1

H 76 5-Cl ls H H 2

CH₃ 77 5-Cl ls H H 2

H 78 5-Cl ls H H 2

CH₃ 79 5-Cl ls H H 2

H 80 5-Cl ls H H 2

CH₃ 81 5-Cl ls H H 2

H 82 5-Cl ls H H 2

CH₃ 83 5-Cl ls H H 2

H 84 5-Cl ls H H 2

CH₃ 85 5-Cl ls H H 2

H 86 5-Cl ls H H 2

CH₃ 87 5-Cl ls H H 2

H 88 5-Cl ls H H 2

CH₃ 89 5-Cl ls H H 2

H 90 5-Cl ls H H 2

CH₃ 91 5-Cl ls H H 2

H 92 5-Cl ls H H 2

CH₃ 93 5-Cl ls H H 2

H 94 5-Cl ls H H 2

CH₃ 95 5-Cl ls H H 2

H 96 5-Cl ls H H 2

CH₃ 97 5-Cl ls H H 2

H 98 5-Cl ls H H 2

CH₃ 99 5-Cl ls H H 2

H 100 5-Cl ls H H 2

CH₃ 101 5-Cl ls H H 2

H 102 5-Cl ls H H 2

CH₃ 103 5-Cl ls H H 2

H 104 5-Cl ls H H 2

CH₃ 105 5-Cl ls H H 2

H 106 5-Cl ls H H 2

CH₃ 107 5-Cl ls H H 2

H 108 5-Cl ls H H 2

CH₃ 109 5-Cl ls H H 2

H 110 5-Cl ls H H 2

CH₃ 111 5-Cl ls H H 2

H 112 5-Cl ls H H 2

CH₃ 113 5-Cl ls H H 2

H 114 5-Cl ls H H 2

CH₃ 115 5-Cl ls H H 2

H 116 5-Cl ls H H 2

CH₃ 117 5-Cl ls H H 2

H 118 5-Cl ls H H 2

CH₃ 119 5-Cl ls H H 2

H 120 5-Cl ls H H 2

CH₃ 121 5-Cl ls H H 2

H 122 5-Cl ls H H 2

CH₃ 123 5-Cl ls H H 2

H 124 5-Cl ls H H 2

CH₃ 125 5-Cl ls H H 2

H 126 5-Cl ls H H 2

CH₃ 127 5-Cl ls H H 2

H 128 5-Cl ls H H 2

CH₃ 129 5-Cl ls H H 2

H 130 5-Cl ls H H 2

CH₃ 131 5-Cl ls H H 2

H 132 5-Cl ls H H 2

CH₃ 133 5-Cl ls H H 2

H 134 5-Cl ls H H 2

CH₃ 135 5-Cl ls H H 2

H 136 5-Cl ls H H 2

CH₃ 137 5-Cl ls H H 2

H 138 5-Cl ls H H 2

CH₃ 139 5-Cl ls H H 2

H 140 5-Cl ls H H 2

CH₃ 141 5-Cl ls H H 2

H 142 5-Cl ls H H 2

CH₃ 143 5-Cl ls H H 2

H 144 5-Cl ls H H 2

CH₃ 145 5-Cl ls H H 2

H 146 5-Cl ls H H 2

CH₃ 147 5-Cl ls H H 2

H 148 5-Cl ls H H 2

CH₃ 149 5-Cl ls H H 2

H 150 5-Cl ls H H 2

CH₃ 151 5-Cl ls H H 2

H 152 5-Cl ls H H 2

CH₃ 153 5-Cl ls H H 2

H 154 5-Cl ls H H 2

CH₃ 155 5-Cl ls H H 2

H 156 5-Cl ls H H 2

CH₃ 157 5-Cl ls H H 2

H 158 5-Cl ls H H 2

CH₃ 159 5-Cl ls H H 2

H 160 5-Cl ls H H 2

CH₃ 161 5-Cl ls H H 2

H 162 5-Cl ls H H 2

CH₃ 163 5-Cl ls H H 2

H 164 5-Cl ls H H 2

CH₃ 165 5-Cl ls H H 2

H 166 5-Cl ls H H 2

CH₃ 167 5-Cl ls H H 2

H 168 5-Cl ls H H 2

CH₃ 169 5-Cl ls H H 2

H 170 5-Cl ls H H 2

CH₃ 171 5-Cl ls H H 2

H 172 5-Cl ls H H 2

CH₃ 173 5-Cl ls H H 2

H 174 5-Cl ls H H 2

CH₃ 175 5-Cl ls H H 2

H 176 5-Cl ls H H 2

CH₃ 177 5-Cl ls H H 2

H 178 5-Cl ls H H 2

CH₃ 179 5-Cl ls H H 2

H 180 5-Cl ls H H 2

CH₃ 181 5-Cl ls H H 2

H 182 5-Cl ls H H 2

CH₃ 183 5-Cl ls H H 2

H 184 5-Cl ls H H 2

CH₃ 185 5-Cl ls H H 2

H 186 5-Cl ls H H 2

CH₃ 187 5-Cl ls H H 2

H 188 5-CF₃ ls H H 2

CH₃ 189 5-CF₃ ls H H 2

H 190 5-Cl ls H H 2

CH₃ 191 5-Cl ls H H 2

H 192 5-Cl ls H H 2

CH₃ 193 5-Cl ls H H 2

H 194 5-Cl ls H H 2

CH₃ 195 5-Cl ls H H 2

H 196 5-Cl ls H H 2

CH₃ 197 5-Cl ls H H 2

H 198 5-CF₃ ls H H 2

CH₃ 199 5-CF₃ ls H H 2

H 200 5-CF₃ ls H H 2

CH₃ 201 5-CF₃ ls H H 2

H 202 5-CF₃ ls H H 2

CH₃ 203 5-CF₃ ls H H 2

H 204 5-CF₃ ls H H 2

CH₃ 205 5-CF₃ ls H H 2

H 206 5-CF₃ ls H H 2

CH₃ 207 5-CF₃ ls H H 2

H 208 5-Cl ls H H 3

CH₃ 209 5-Cl ls H H 3

H 210 5-Cl O CH₃ CH₃ 1

CH₃ 211 5-Cl O CH₃ CH₃ 1

H 212 5-Cl O CH₃ CH₃ 1

CH₃ 213 5-Cl O CH₃ CH₃ 1

H 214 5-Cl O CH₃ CH₃ 1

CH₃ 215 5-Cl O CH₃ CH₃ 1

H 216 5-Cl O CH₃ CH₃ 1

CH₃ 217 5-Cl O CH₃ CH₃ 1

H 218 5-Cl O CH₃ CH₃ 1

CH₃ 219 5-Cl O CH₃ CH₃ 1

H 220 5-Cl O CH₃ CH₃ 1

CH₃ 221 5-Cl O CH₃ CH₃ 1

H 222 5-Cl O CH₃ CH₃ 1

CH₃ 223 5-Cl O CH₃ CH₃ 1

H 224 5-Cl O CH₃ CH₃ 1

CH₃ 225 5-Cl O CH₃ CH₃ 1

H 226 5-Cl O CH₃ CH₃ 1

CH₃ 227 5-Cl O CH₃ CH₃ 1

H 228 5-Cl O CH₃ CH₃ 1

CH₃ 229 5-Cl O CH₃ CH₃ 1

H 230 5-Cl O CH₃ CH₃ 1

CH₃ 231 5-Cl O CH₃ CH₃ 1

H 232 5-Cl O CH₃ CH₃ 1

CH₃ 233 5-Cl O CH₃ CH₃ 1

H 234 5-Cl O CH_(3 (S)) H 1

C₂H₅ 235 5-Cl O CH_(3 (S)) H 1

H 236 5-Cl O CH_(3 (R)) H 1

CH₃ 237 5-Cl O CH_(3 (R)) H 1

H 238 5-CF₃ O CH_(3 (S)) H 1

C₂H₅ 239 5-CF₃ O CH_(3 (S)) H 1

H 240 5-CF₃ O CH_(3 (R)) H 1

CH₃ 241 5-CF₃ O CH_(3 (R)) H 1

H 242 5-CH₃ ls H H 1

CH₃ 243 5-CH₃ ls H H 1

H 244 5-OMe ls H H 1

CH₃ 245 5-OMe ls H H 1

H 246 5-OMe ls H H 2

CH₃ 247 5-OMe ls H H 2

H 248 5-CH₃ ls H H 2

CH₃ 249 5-CH₃ ls H H 2

H 250 5-CH₃ ls H H 2

CH₃ 251 5-CH₃ ls H H 2

H 252 5-Cl ls H H 2

CH₃ 253 5-Cl ls H H 2

H 254 5-Cl ls H H 2

CH₃ 255 5-Cl ls H H 2

H 256 5-Cl ls H H 3

CH₃ 257 5-Cl ls H H 3

H 258 5-Cl ls H H 3

CH₃ 259 5-Cl ls H H 3

H 260 5-Cl ls CH₃ CH₃ 2

H 261 5-Cl ls CH₃ CH₃ 2

H 262 5-CF₃ ls H H 2

CH₃ 263 5-CF₃ ls H H 2

H 264 5-CF₃ ls H H 2

CH₃ 265 5-CF₃ ls H H 2

H 266 5-CF₃ ls H H 2

CH₃ 267 5-CF₃ ls H H 2

H 268 5-CF₃ ls H H 2

CH₃ 269 5-CF₃ ls H H 2

H 270 5-Cl ls H H 2

CH₃ 271 5-Cl ls H H 2

CH₃ 272 5-Cl ls H H 2

H 273 5-Cl ls H H 2

CH₃ 274 5-Cl ls H H 2

H 275 5-Cl ls H H 2

CH₃ 276 5-Cl ls H H 2

H 277 5-Cl ls H H 2

CH₃ 278 5-Cl ls H H 2

CH₃ 279 5-Cl ls H H 2

CH₃ 280 5-Cl ls H H 2

CH₃ 281 5-Cl ls H H 2

H 282 5-Cl ls H H 2

CH₃ 283 5-Cl ls H H 2

H 284 5-Cl ls H H 2

CH₃ 285 5-Cl ls H H 2

H 286 5-Cl ls H H 2

CH₃ 287 5-Cl ls H H 2

H 288 5-Cl ls H H 2

CH₃ 289 5-Cl ls H H 2

H 290 5-Cl ls H H 2

CH₃ 291 5-Cl ls H H 2

H 292 5-Cl ls H H 2

CH₃ 293 5-Cl ls H H 2

H 294 5-Cl ls H H 2

CH₃ 295 5-Cl ls H H 2

CH₃ 296 5-Cl ls H H 2

H 297 5-Cl ls H H 2

CH₃ 298 5-Cl ls H H 2

CH₃ 299 5-Cl ls H H 2

CH₃ 300 5-Cl ls H H 2

H 301 5-Cl ls H H 2

H 302 5-Cl ls H H 1

H 303 5-Cl ls H H 2

CH₃ 304 5-Cl ls H H 2

CH₃ 305 5-Cl ls H H 2

H 306 5-Cl ls H H 2

CH₃ 307 5-Cl ls H H 2

CH₃ 308 5-Cl ls H H 2

H 309 5-Cl ls H H 2

CH₃ 310 5-Cl ls H H 2

H ^(*)“ls” means: single bond, and Ac represents the acetyl group

Pharmacological Activity

The compounds of the invention were subjected to biological tests so asto evaluate their potential for treating or preventing certainpathologies. In a first stage, the capacity of the compounds to behaveas PPAR nuclear receptor activators was measured. A transactivation testis used as primary screening test. Cos-7 cells are transfected with aplasmid that expresses a construct of a murine or human PPAR-Gal4receptor (PPARα-Gal4 or PPARδ-Gal4 or PPARγ-Gal4 receptor) and areporter plasmid 5Gal4pGL3 TK Luc. The transfections are performed usinga chemical agent (Jet PEI). The transfected cells are distributed in384-well plates and left to stand for 24 hours. After 24 hours, theculture medium is changed. The test products are added (finalconcentration of between 10⁻⁴ and 3×10⁻¹⁰ M) to the culture medium.After incubating overnight, the luciferase expression is measured afteraddition of “SteadyGlo” according to the manufacturer's instructions(Promega). Fenofibric acid at 10⁻⁵ M (PPARα agonist), GW501516 at 10⁻⁸ M(PPARδ agonist) and rosiglitazone at 10⁻⁶ M (PPARγ agonist) are used asreferences. The results are expressed as a level of induction (number oftimes) compared with the basal level as a percentage of activity of theadequate reference (reference=100%). The effect-concentration curves andthe EC₅₀ values are calculated using the Assay Explorer software (MDL).The compounds according to the invention have a level of inductionranging up to 319% (PPARα), 151% (PPARδ) and 114% (PPARγ). The compoundsaccording to the invention have an EC₅₀ of between 4 nM and 1500 nM.

A second series of tests was performed with the compounds according tothe invention, with the aim of confirming the activity deduced fromtheir affinity for the receptors mentioned previously. This testconsists in measuring the β-oxidation on cells of human hepatic originHuH7 and cells of murine muscle origin C2C12 after differentiation asmyotubes. The cells are inoculated in Petri dishes comprising a centralwell. The products are added to the culture medium and incubated for 48hours at different concentrations. After incubation for 22 hours,¹⁴C-radiolabeled oleate (oleate 1-C14) is added to the culture medium.The β-oxidation reaction is stopped two hours later by adding 40%perchloric acid. The CO₂ released during the oxidation of the oleate istrapped with KOH solution and then counted. Each test is performed threetimes. The results are expressed as a percentage of variation relativeto the control dishes (dishes without compounds). According to thistest, the compounds according to the invention increase the β-oxidationby up to +145% at a concentration of 10 μM on HuH7 cells. Theβ-oxidation is also increased by 70% in the presence, for example, ofthe compound according to Example 10 used at a concentration of 10 μMduring a test on C2C12 cells.

Certain compounds according to the invention were tested on a model ofdb/db mice in order to confirm their potential as active principle. Thetest protocol is as follows:

Homozygous male C57BL/Ks-db mice (db/db mice), 11-13 weeks old at thestart of the studies, are divided into groups of 9-10 animals. Theproducts are administered orally, once a day for 5 days. A group of micereceives the vehicle alone (methylcellulose solution at 0.5% or 1%). Ablood sample is taken from the retro-orbital sinus before treatment and4 hours after the final gavage. After centrifugation, the serum iscollected and the levels of cholesterol, triglycerides and glucose aremeasured using a multiparameter analyzer with commercial products. Theresults are expressed as a percentage of variation on the final dayrelative to the control group. By way of example, a number of resultsobtained with the compounds according to the invention are given in thefollowing table, in comparison with fenofibrate or rosiglitazone:

Pharmacological activity Compound Assay (mg/kg) Glucose TriglyceridesCholesterol Fenofibrate 100 −9 −7 +32 Rosiglitazone 3 −41 −52 −30 Ex. 210 −36 −32 +41 Ex. 20 10 −72 −65 +13 Ex. 4 10 −57 −45 +4 Ex. 293 10 −24−15 +16 Ex. 259 10 −51 −16 +32

These results, which are in accordance with the modifications expectedfrom PPAR nuclear receptor activators, confirm the value of thecompounds according to the invention for their use as active principlesof medicaments for human use for preventing or treatinghypertriglyceridemia, hypercholesterolemia and obesity, and, moregenerally, for re-establishing normal parameters during a disruption inlipid and carbohydrate metabolism. The compounds according to theinvention also find their use in the case of treating endothelialdysfunction, inflammatory diseases or neurodegenerative diseases.

The invention also relates to pharmaceutical compositions for preventingor treating the diseases mentioned above, when they contain, as activeprinciple, at least one of the compounds of formula I according to theinvention.

These pharmaceutical compositions may be prepared in a conventionalmanner, using pharmaceutically acceptable excipients, so as to obtainforms that may preferably be administered orally, for example tablets orgel capsules.

In practice, in the case of oral administration of the compound, thedaily dosage in man will preferably be between 5 and 500 mg.

The foregoing description and examples have been set forth merely toillustrate the invention and are not intended to be limiting. Sincemodifications of the described embodiments incorporating the spirit andsubstance of the invention may occur to persons skilled in the art, theinvention should be construed broadly to include all variations withinthe scope of the appended claims and equivalents thereof.

1. A method of activating PPAR receptors in a subject, said methodcomprising administering to said subject an effective PPAR receptoractivating amount of a pyrrolopyridine compound corresponding to formulaI:

wherein R₁ and R₂ each independently represent hydrogen, halogen, C₁-C₃alkyl, C₁-C₄ alkoxy or CF₃; R₃ and R₄ each independently representhydrogen or C₁-C₄ alkyl; R represents hydrogen or C₁-C₃ alkyl; nrepresents 1, 2 or 3; X represents a single bond or an oxygen atom, andAr represents an aromatic or heteroaromatic nucleus selected from thegroup consisting of phenyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl,isoxazolyl, furyl, thienyl, pyrrolyl, pyridyl, biphenyl, naphthyl,1,2,3,4-tetrahydronaphthyl, quinolyl, isoquinolyl,1,2,3,4-tetrahydroquinolyl, benzimidazolyl, benzopyrazinyl, indolyl,2,3-dihydroindolyl, benzofuryl, 2,3-dihydrobenzofuryl, benzothiazolyl,benzothiadiazolyl, benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl,1,3-benzodioxolyl, 2,3-dihydrobenzodioxinyl, imidazothiazolyl andbenzoxazolyl groups, optionally substituted with one or moresubstituents selected from the group consisting of halogen, C₁-C₆ alkyl,C₁-C₄ alkoxy, trifluoromethyl, trifluoromethoxy, nitro, acetyl,acetylamino, dialkylamino, amino, oxazolyl, thiazolyl, pyrazolyl,pyrrolidinyl, pyridyl, pyrimidinyl, methylpyrimidinyl and morpholinyl,or a pharmaceutically acceptable salt thereof.
 2. A method as claimed inclaim 1, wherein Ar represents an aromatic or heteroaromatic nucleusselected from the group consisting of phenyl, pyridyl, biphenyl,naphthyl, quinolyl, benzopyrazinyl, indolyl, 2,3-dihydroindolyl,benzofuryl, 2,3-dihydrobenzofuryl, benzothiazolyl, benzothiadiazolyl,benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl, 1,3-benzodioxolyl,2,3-dihydrobenzodioxinyl, imidazothiazolyl and benzoxazolyl groups,optionally substituted with one or more substituents selected from thegroup consisting of halogen, C₁-C₆ alkyl, C₁-C₄ alkoxy, trifluoromethyl,trifluoromethoxy, nitro, acetyl, acetylamino, dialkylamino, amino,oxazolyl, thiazolyl, pyrazolyl, pyrrolidinyl, pyridyl, pyrimidinyl,methylpyrimidinyl or morpholinyl.
 3. A method as claimed in claim 1,wherein R₁ represents chlorine or trifluoromethyl.
 4. A method asclaimed in claim 1, wherein said compound is administered in the form ofa pharmaceutical composition further comprising at least onepharmaceutically acceptable carrier or adjuvant.
 5. A method of treatinga condition selected from the group consisting of atherosclerosis,myocardial infarction, hypertension and cerebral vascular disease in asubject, said method comprising activating PPAR receptors in saidsubject by administering to said subject an effective PPAR receptoractivating amount of a pyrrolopyridine compound corresponding to formulaI:

wherein R₁ and R₂ each independently represent hydrogen, halogen, C₁-C₃alkyl, C₁-C₄ alkoxy or CF₃; R₃ and R₄ each independently representhydrogen or C₁-C₄ alkyl; R represents hydrogen or C₁-C₃ alkyl; nrepresents 1, 2 or 3; X represents a single bond or an oxygen atom, andAr represents an aromatic or heteroaromatic nucleus selected from thegroup consisting of phenyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl,isoxazolyl, furyl, thienyl, pyrrolyl, pyridyl, biphenyl, naphthyl,1,2,3,4-tetrahydronaphthyl, quinolyl, isoquinolyl,1,2,3,4-tetrahydroquinolyl, benzimidazolyl, benzopyrazinyl, indolyl,2,3-dihydroindolyl, benzofuryl, 2,3-dihydrobenzofuryl, benzothiazolyl,benzothiadiazolyl, benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl,1,3-benzodioxolyl, 2,3-dihydrobenzodioxinyl, imidazothiazolyl andbenzoxazolyl groups, optionally substituted with one or moresubstituents selected from the group consisting of halogen, C₁-C₆ alkyl,C₁-C₄ alkoxy, trifluoromethyl, trifluoromethoxy, nitro, acetyl,acetylamino, dialkylamino, amino, oxazolyl, thiazolyl, pyrazolyl,pyrrolidinyl, pyridyl, pyrimidinyl, methylpyrimidinyl and morpholinyl,or a pharmaceutically acceptable salt thereof.
 6. A method as claimed inclaim 5, wherein Ar represents an aromatic or heteroaromatic nucleusselected from the group consisting of phenyl, pyridyl, biphenyl,naphthyl, quinolyl, benzopyrazinyl, indolyl, 2,3-dihydroindolyl,benzofuryl, 2,3-dihydrobenzofuryl, benzothiazolyl, benzothiadiazolyl,benzisoxazolyl, 3,4-dihydro-1,4-benzoxazinyl, 1,3-benzodioxolyl,2,3-dihydrobenzodioxinyl, imidazothiazolyl and benzoxazolyl groups,optionally substituted with one or more substituents selected from thegroup consisting of halogen, C₁-C₆ alkyl, C₁-C₄ alkoxy, trifluoromethyl,trifluoromethoxy, nitro, acetyl, acetylamino, dialkylamino, amino,oxazolyl, thiazolyl, pyrazolyl, pyrrolidinyl, pyridyl, pyrimidinyl,methylpyrimidinyl or morpholinyl.
 7. A method as claimed in claim 5,wherein R₁ represents chlorine or trifluoromethyl.
 8. A method asclaimed in claim 5, wherein said compound is administered in the form ofa pharmaceutical composition further comprising at least onepharmaceutically acceptable carrier or adjuvant.
 9. A method as claimedin claim 5, wherein said condition is atheroxclerosis.
 10. A method asclaimed in claim 5, wherein said condition is myocardial infarction. 11.A method as claimed in claim 5, wherein said condition is hypertension.12. A method as claimed in claim 5, wherein said condition is cerebralvascular disease.